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Biomedical subjects

M K Edwards

Publications and source records attributed to M K Edwards.

At least 55 records · Page 3Linked to original sources

The concentration of retinoic acid determines the differentiated cell types formed by a teratocarcinoma cell line.

Retinoic acid (RA) can induce the differentiation of teratocarcinoma cells in culture (S. Strickland and V. Mahdavi, 1978, Cell 15, 393-403; E. M. V. Jones-Villeneuve, M. W. McBurney, K. A. Rogers, and V. I. Kalnins, 1982, J. Cell. Biol. 94, 253-262). With the teratocarcinoma cell line, P19S1801A1 (O1A1), the differentiated cell types formed from cell aggregates exposed to RA are dependent on the concentration of drug used in the treatment. Cultures exposed to low concentrations (10(-9)M) are characterized by an abundance of cardiac muscle. Skeletal muscle becomes abundant at higher drug concentrations (10(-8)M) with neurons and astroglia appearing at very high concentrations (10(-7) to 10(-5) M). These results suggest that during normal embryogenesis, the commitment of pluripotent cells to particular developmental avenues may be determined in part by concentration gradients of substances such as retinoids.

Animals↗

Induced muscle differentiation in an embryonal carcinoma cell line.

Cells of the teratocarcinoma-derived line P19S1801A1 (01A1) are pluripotent embryonal carcinoma cells and can be induced to differentiate when aggregated and exposed to dimethyl sulfoxide. Many nonneural cell types appear in dimethyl sulfoxide-treated cultures, cardiac and skeletal muscle being the most easily identified. We have used immunofluorescence procedures with monoclonal antibodies directed against muscle myosin to confirm and quantitate the number of muscle cells formed. A monoclonal antibody reactive with an embryonal carcinoma-specific surface antigen was used to confirm the disappearance of undifferentiated cells after dimethyl sulfoxide treatment. Cardiac muscle cells developed within 4 to 5 days of drug exposure, but skeletal muscle cells did not become evident until 7 to 8 days. We have isolated a mutant cell line (D3) which appears to be incapable of muscle development but which does form neurons and glial cells when exposed to high retinoic acid concentrations. We propose that this system will be useful for investigation of the means by which pluripotent cells become committed to development along the striated muscle lineages.

Animals↗

Control of muscle and neuronal differentiation in a cultured embryonal carcinoma cell line.

Pluripotent murine embryonal carcinoma cells can differentiate in culture into many tissue types similar to those normally found in early embryos and may be useful in investigating some developmental events. Central to our understanding of embryonic development are explanations of cellular determination, that is, the commitment of early embryonic cells to form divergent cell types. Of relevance is recent work with the F9 line of embryonal carcinoma cells which suggests that certain extra-embryonic cell types are specifically formed following treatment of undifferentiated cells with drugs and the manipulation of culture conditions. We report here that the P19 line of embryonic carcinoma cells may provide and analogous system in which drugs can be used to manipulate the formation of tissues which normally comprise the fetus. In the presence of dimethyl sulphoxide (DMSO) aggregates of P19 cells differentiate rapidly to form large amounts of cardiac and skeletal muscle but no neurones or glia. We have previously shown that in the presence of high concentrations of retinoic acid (greater than 5 x 10(-7) M), aggregates of these same cells develop into neuronal and glial tissues but not muscle. Thus, drugs can be used to generate two quite different spectra of embryonic tissue types from the same population of embryonal carcinoma cells.

Actins↗

Invasive orbital pseudotumor--CT demonstration of extension beyond orbit.

Two cases of orbital pseudotumor are described with computed tomographic (CT) studies showing extension of the pseudotumor beyond the confines of the bony orbit. In one patient with orbital pseudotumor involving the medial rectus muscle, the pseudotumor extended through the medial wall of the orbit into the ethmoid sinus. A second patient had extension of orbital pseudotumor into the infraorbital fissure causing enlargement of the infraorbital fissure and foramen. Both lesions were confirmed by biopsy.

Adult↗

Cribside neurosonography: real-time sonography for intracranial investigation of the neonate.

A prospective study was made of 94 real-time sonographic sector scans of 56 neonates in a 6 month period. The examinations were performed using the anterior fontanelle as an acoustic window. In 17 cases, computed tomography (CT) head scans were available for comparison. In no case did the CT and sonographic examination disagree as to the size of the lateral ventricles. Abnormalities detected by sonography include ventriculomegaly, intracerebral hematomas, a congenital glioma, and several cystic lesions. Sonographic sector scanning produces excellent, detailed images of dilated lateral and third ventricles, uses no ionizing radiation, is less expensive than CT, and can be performed in the isolette, minimizing the risk of hypoxia and hypothermia. At Methodist Hospital Graduate Medical Center, sonography has replaced CT as the initial method of investigation of ventricular size. CT plays a complementary role in the evaluation of the posterior fossa, intracranial hemorrhage, and mass lesions.

Cerebral Arteries↗

Three-dimensional structure of the central mitotic spindle of Diatoma vulgare.

Central mitotic spindles in Diatoma vulgare have been investigated using serial sections and electron microscopy. Spindles at both early stages (before metaphase) and later stages of mitosis (metaphase to telophase) have been analyzed. We have used computer graphics technology to facilitate the analysis and to produce stereo images of the central spindle reconstructed in three dimensions. We find that at prometaphase, when the nuclear envelope is dissassembling, the spindle is constructed from two sets of polar microtubules (MTs) that interdigitate to form a zone of overlap. As the chromosomes become organized into the metaphase configuration, the polar MTs, the spindle, and the zone of overlap all elongate, while the number of MTs in the central spindle decreases from greater than 700 to approximately 250. Most of the tubules lost are short ones that reside near the spindle poles. The previously described decrease in the length of the zone of overlap during anaphase central spindle elongation is clearly demonstrated in stereo images. In addition, we have used our three-dimensional data to determine the lengths of the spindle MTs at various times during mitotis. The distribution of lengths is bimodal during prometaphase, but the short tubules disappear and the long tubules elongate as mitosis proceeds. The distributions of MT lengths are compared to the length distributions of MTs polymerized in vitro, and a model is presented to account for our findings about both MT length changes and microtubule movements.

Anaphase↗

Cross-sectional structure of the central mitotic spindle of Diatoma vulgare. Evidence for specific interactions between antiparallel microtubules.

During the transition from prometaphase to metaphase, the cross-sectional area of the central spindle of Diatoma decreases by a factor of nearly two, both at the poles and at the region of overlapping microtubules (MTs) near the spindle equator. The density of spindle MT packing stays approximately constant throughout mitosis. Optical diffraction analysis of electron micrographs shows that the packing of the MTs at the poles at all stages of mitosis is similar to that expected for a two-dimensional liquid. Analysis of the region of overlap reveals more packing regularity: during prometaphase, a square packing emerges that displays sufficient organization by late metaphase to generate five orders of diffraction; during anaphase the packing in the overlap region shifts to hexagonal; at telophase, it returns to square. From the data provided by serial section reconstructions of the central spindle, it is possible to identify the polarity of almost every spindle MT, that is, to identify one pole with which the MT is associated. Near neighbor analyses of MTs in cross sections of the overlap region show that MTs prefer antiparallel near neighbors. These near neighbors are most often found at a spacing of approximately 40 nm center-to-center, while parallel near neighbors in the zone of overlap are spaced essentially at random. These results are evidence for a specific interaction between antiparallel MTs. In some sections definite bridges between MTs can be seen. Our findings show that certain necessary conditions for a sliding filament model of anaphase spindle elongation are met.

Anaphase↗

MR imaging of central pontine myelinolysis.

Central pontine myelinolysis is a demyelinating disorder with characteristic magnetic resonance features. Findings on T1-weighted scans include a symmetric region of low signal involving the basilar pons with sparing of the descending corticospinal tracts as well as the peripheral pontine tissues. The T2-weighted images show an area of high signal corresponding to the abnormal region identified on T1-weighted scans. Associated extrapontine demyelinating lesions are also demonstrated.

Demyelinating Diseases↗

Reversible cerebral lesions associated with tiazofurin usage: MR demonstration.

Tiazofurin is an experimental chemotherapeutic agent currently undergoing clinical evaluation. We report our results with magnetic resonance (MR) in demonstrating reversible cerebral abnormalities concurrent with the use of this drug. The abnormalities on MR were correlated with findings on CT as well as with cerebral angiography. The utility of MR in the evaluation of patients receiving this new agent is illustrated.

Antineoplastic Agents↗

Toxoplasmic myelitis in AIDS: gadolinium-enhanced MR.

An acquired immunodeficiency syndrome (AIDS) patient developed acute symptoms suggestive of a lower spinal cord lesion. Magnetic resonance imaging was performed and demonstrated an enhancing lesion of the conus medullaris. Surgical biopsy revealed Toxoplasma gondii. Disease processes involving the spinal cord in AIDS patients are reviewed and differential diagnosis for the lesion in this patient is discussed.

Acquired Immunodeficiency Syndrome↗

Gadolinium enhancement in acute disseminated encephalomyelitis.

Acute disseminated encephalomyelitis (ADEM) is a widespread CNS inflammation that usually follows an infection or vaccination. We present a case of ADEM, which in addition to the typical MR findings, demonstrates gadolinium enhancement of several of the lesions. Since ADEM is usually a monophasic illness, it has been postulated that all lesions might enhance with paramagnetic contrast medium since they would all be expected to be active. Our case demonstrates enhancement of some of the lesions, without enhancement of others.

Acute Disease↗

MRI of Guillain-Barré syndrome.

We describe the results of MRI of the spine in a case of Guillain-Barré syndrome. The main finding was abnormal enhancement of the nerve roots in the region of the conus medullaris and cauda equina.

Cauda Equina↗

MR of intracranial Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is a disease of children characterized by idiopathic proliferation of histiocytes in the reticuloendothelial system. Intracranial LCH involving the brain is uncommon. We present a case of LCH involving the dural venous sinuses and choroid plexus. Contrast MRI provided an excellent means of identifying the extent of tumor involvement and showed that the patient was at risk for venous sinus thrombosis.

Adolescent↗

Magnetic resonance evaluation of pediatric spinal dysraphism.

Magnetic resonance (MR) scans of 22 children with spinal dysraphism were reviewed. MR scans of the cervicothoracic spine in 12 cases revealed 10 Chiari II malformations, 1 Chiari III malformations, and 4 syringohydromyelias. Twelve MR scans of the lumbosacral region were performed demonstrating 11 tethered cords, 6 myelomeningoceles, 4 lipomyeloschises, 2 diastematomyelias, 2 syringohydromyelias, and 2 dermal sinus tracts. MR is effective in defining the relationship of the cerebellar tonsils and brainstem to the upper cervical spinal canal and in evaluating the extent of syringohydromyelia and the degree of cord expansion. The ability to image the spinal cord and associated paraspinal lesions directly in the sagittal and coronal planes with excellent tissue characterization allows MR to accurately diagnose and define the myriad abnormalities associated with pediatric dysraphism.

Adolescent↗

Magnetic resonance imaging diagnosis of a cerebral aneurysm in an infant. Case report and review of the literature.

A posterior cerebral artery aneurysm presented as a seizure disorder in a 7-week-old infant. A small hemorrhage in the posterior thalamus was seen on CT scan. However, magnetic resonance imaging (MRI study) demonstrated an aneurysm and appropriate therapy was carried out. The incidence, natural history, etiology, and surgical treatment of these lesions are reviewed, and the usefulness of MRI in their diagnosis is emphasized.

Cerebral Angiography↗