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Biomedical subjects

M E Smith

Publications and source records attributed to M E Smith.

At least 289 records · Page 16Linked to original sources

The cdc30 mutation in Saccharomyces cerevisiae affects phosphoglucose isomerase, the cell cycle and sporulation.

Spontaneous revertants of the cdc30 mutation in Saccharomyces cerevisiae simultaneously regained the ability to grow and divide at 36.5 degrees C on glucose-containing media along with a more thermostable phosphoglucose isomerase (PGI). An independently isolated allele of cdc30 gave a similar phenotype to that previously described including temperature-sensitivity of PGI. Isoelectric focussing allowed the separation of two isoenzymes of PGI. These results all support the idea that two genes--PGI1 and CDC30--are responsible for PGI activity in yeast. Diploid strains homozygous for the cdc30 mutation sporulated poorly in potassium acetate irrespective of whether the cells had previously been cultured at a temperature that was permissive or restrictive for cell cycle progression. This was not surprising because a strain defective in PGI would not be expected to be able to complete the gluconeogenic events of sporulation.

Alleles↗

Effect of soluble factors from nerve and muscle on alpha-bungarotoxin binding sites in isolated sarcolemmal membranes of the rat.

1. Sarcolemmal membranes were isolated from normal and from denervated muscles and the specific binding of [125I]-alpha-bungarotoxin to the membranes was determined. 2. Cytosol prepared from either slow (soleus) or fast (extensor digitorum longus) muscle increased the toxin binding. Similar effects were seen with cytosol from muscles which had been denervated 5 to 7 days previously and with cytosol from sciatic nerve. A purified preparation of a bacterial phospholipase C also produced this effect. 3. Bathing medium in which normal or denervated muscles had been incubated, increased the toxin binding to normal membranes, but the normal bathing medium decreased the binding to membranes prepared from denervated muscles. 4. The possibility that pre-existing latent acetylcholine receptors can be activated by intracellular factors released from muscles is discussed.

Animals↗

Ethanol decreases entry of vincristine into brain of rat: modification by acetylcholine or histamine.

Male Sprague-Dawley rats were anesthetized with pentobarbital sodium and a jugular vein and femoral artery cannulated. Ethanol (3%; 13.3 ml/kg) was injected intraperitoneally 5 min before the administration of 10 microCi [3H]vincristine sulfate intravenously. One minute later, saline, acetylcholine, (1 or 2 micrograms/kg) or histamine (1.25, 2.5 or 5 micrograms/kg) was given intravenously. At 15 min the thoracic cavity was opened, a cardiac sample of blood obtained, and saline infused into the left ventricle to remove blood from the brain. Samples of the cerebral cortex, midbrain, cerebellum, and plasma were subjected to liquid scintillation counting. The concentration of ethanol at 20 min after its administration was 20.3 mg/dl. This was associated with a significant decrease in radioactivity in the cerebral cortex and midbrain and a nonsignificant decrease in the cerebellum. Administration of 2 micrograms/kg of acetylcholine in the presence of ethanol decreased the blood pressure and increased the movement of radioactivity into the cerebral cortex and cerebellum while causing a significant decrease in the midbrain. Histamine (2.5 micrograms/kg) significantly increased the movement into the cerebellum and 5 micrograms/kg decreased the movement into the midbrain. The permeability of the blood-brain barrier to [3H]vincristine was decreased by ethanol and this could be modified regionally by vasoactive doses of acetylcholine and histamine. Possible therapeutic advantage might result if vincristine were given in the presence of ethanol which should diminish the potential neurotoxicity.

Acetylcholine↗

Action of phospholipase C at the neuromuscular junction in rodent skeletal muscles.

The isometric tension developed in response to diffuse application of acetylcholine was recorded in intact soleus muscles of the rat. Purified bacterial phospholipases of the C type, which hydrolyse either phosphatidylinositol or phosphatidylcholine, increased the acetylcholine contracture responses of the muscles. Sciatic nerve cytosol which had been purified over 8-fold with respect to phosphatidylinositol phospholipase C activity also increased these responses. The effect of phospholipase C on the miniature endplate potentials and neurally evoked endplate potentials was investigated in mouse diaphragm in vitro. The amplitude of both the miniature endplate potentials and the evoked endplate potentials was increased by the enzyme. The resting membrane potential, the effective input resistance and the frequency of miniature endplate potentials were not significantly altered by concentrations of the enzyme which increased the endplate responses. It is suggested that phospholipase C could have a trophic role at the neuromuscular junction.

Animals↗

Exposure of receptor sites on rat muscle membranes by a neurally released factor.

Isolated phrenic nerve-diaphragm preparations of the rat were stimulated electrically via the nerve. The medium bathing the preparation contained a factor which increased the specific binding (Bmax) of [125I]alpha-bungarotoxin to isolated sarcolemmal membranes. Medium from control preparations, left unstimulated, had no significant effect on the binding. The nerve stumps in the stimulated preparations were relatively depleted of the factor which increased the binding. The possibility that latent acetylcholine receptors are exposed by a factor released from the nerve during impulse activity is suggested.

Animals↗

Important risk factors for death in adults: a 10-year follow-up of the Nutrition Canada survey cohort.

Data on mortality among over 8000 Canadians aged 35 to 79 years who participated in the Nutrition Canada survey are presented. The effects of various risk factors on mortality were assessed with a multivariate Poisson regression analysis. Factors associated with a significantly increased risk of death over a 10-year follow-up period ending in 1981 included cigarette smoking, hypertension and diabetes mellitus. A shallow U-shaped mortality pattern was observed for body mass index and for serum cholesterol level. No statistically significant increases in risk were associated with alcohol consumption. The population attributable risks for smoking, hypertension and diabetes were 39%, 8% and 6% respectively for men and 21%, 12% and 7% respectively for women.

Adult↗

Astrocytoma of the ciliary body.

A healthy 24-year-old man was noted to have rubeosis iridis and a ciliary body mass. Iridocyclectomy successfully removed the lesion with preservation of vision and resolution of rubeosis. Histologic and immunocytochemical examinations revealed a glial tumor of the ciliary epithelium.

Adult↗

ReCAP: the Registry of Cytogenetic Abnormalities and Phenylketonuria.

The Registry of Cytogenetic Abnormalities and Phenylketonuria (ReCAP) is a multicenter collaborative registry of information on patients with constitutional cytogenetic abnormalities or hyperphenylalaninemia (HPA). Data are entered by microcomputer at four contributing centers. Records are then electronically transmitted to the coordinating center, where the composite cytogenetic and hyperphenylalaninemia databases are maintained on a mainframe computer. A set of programs, known as the ReCAP ISCN Translator, is used to create additional database records describing in detail the chromosome abnormalities present in each patient. The ReCAP computer system permits rapid and flexible retrieval of cases on the basis of any combination of laboratory, clinical, psychometric, or genetic characteristics contained within the databases. Special procedures protect patient confidentiality and assure that ReCAP data are of consistently high quality. Qualified investigators may use ReCAP as a resource for a variety of scientific studies.

Chromosome Aberrations↗

Glial fibrillary acidic protein in chronic relapsing experimental allergic encephalomyelitis in SJL/J mice.

The gliotic scar in the demyelinated plaque is a prominent feature of the pathology of multiple sclerosis. Chronic relapsing experimental allergic encephalomyelitis (EAE) in the SJL/J mouse has many characteristics in common with multiple sclerosis in the human, including the development of intense gliosis during the course of the demyelinating disease. With the use of antibody to the astrocyte marker glial fibrillary acidic protein (GFAP) we have measured the increase of GFAP over an 11-month course of chronic EAE. Intense staining of astrocyte fibers was seen around EAE lesions, which were most frequently observed in the cerebellum, periventricular areas, and in the spinal cord. The relative amount of GFAP was estimated by preparation of cytoskeletal proteins from the affected CNS areas, separation of proteins by polyacrylamide gel electrophoresis, and quantitation of GFAP in relation to the 70-kD neurofilament protein (NF) in gel scans. The ratio GFAP/70-kD NF protein in control animals did not change significantly over 11 months, whereas this ratio gradually increased to 2.54 in animals with chronic relapsing EAE 6 months after immunization. Although some decrease of neural fibers may have contributed partially to this change in ratio, the amounts of GFAP were greatly increased. These results indicate that the SJL/J mouse with chronic relapsing EAE provides an excellent model with which to investigate the formation and development of the gliotic plaque analogous to that seen in demyelinated areas in multiple sclerosis tissue.

Animals↗

Antibody to myelin constituents: a possible factor in induction of cell-mediated demyelination.

Results from this laboratory have demonstrated that 14C-labeled myelin opsonized with antibodies raised to purified CNS myelin in rabbit is phagocytized by cultured macrophages in larger amounts than untreated myelin or myelin opsonized with preimmune serum. The cultured macrophages produced high amounts of radioactive cholesterol ester and triglyceride from the antibody-treated myelin while much less was formed from preimmune serum-treated or untreated myelin. Antiserum to galactocerebroside also greatly enhanced the formation of radioactive cholesterol ester, while that to myelin basic protein as well as to other myelin constituents had little or no effect. Serum from Lewis rats with acute EAE 13-14 days after immunization with whole CNS myelin also stimulated radioactive cholesterol ester formation compared to serum from Freund's adjuvant-injected controls (FAC). Serum from EAE rats as a result of myelin basic protein injection was as active as that from rats with whole myelin injection. No galactocerebroside antibody could be demonstrated in the EAE sera, although a strong immunostaining to myelin basic protein and proteolipid protein was demonstrated. IgG prepared from EAE serum also showed stimulatory effects compared to IgG from FAC serum, but much of the activity was lost, and the possibility that other factors may be involved is discussed. These experiments provide evidence that myelin phagocytosis and digestion by macrophages is enhanced by the presence of antibody to myelin. In EAE this antibody may leak into CNS with the breakdown of the blood-brain barrier.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A guide to the use of simple process measures.

Monitoring treatment process can be an overwhelming and time consuming task for an evaluator in a small agency or a large agency. However, the amount of time allocated to this process can be minimized by developing and utilizing a limited set of treatment process indicators for monitoring purposes. This paper describes nine indicators that have been used successfully to monitor treatment process at a hospital based Community Mental Health Center. Each indicator is discussed in terms of the problem that the indicator addresses, typical data collection problems that may occur, the utility of the indicator and the limitations that should be considered when interpreting the data.

Community Mental Health Centers↗

Magnetic resonance imaging in the evaluation of optic nerve gliomas.

Five patients with optic nerve gliomas were evaluated by magnetic resonance imaging (MRI). Images obtained with MRI were equal to computed tomography (CT) in evaluation of the orbital components of these tumors and superior to CT in evaluating the intracanalicular, chiasmal, and post-chiasmal extension of tumor. MRI is unimpeded by artifacts produced by surrounding bone, as encountered in CT, and also proves to be more sensitive in delineating subtle differences in fat content and hydration of neural tissues. Thus, MRI is extremely valuable in furthering our understanding of the natural and therapeutic response of optic nerve gliomas.

Adult↗

Retinoblastoma with anterior chamber extension.

Anterior chamber retinoblastoma is a rare clinical entity. The authors have reviewed the records of 1500 patients with retinoblastoma to determine the incidence and prognostic ramifications. Of 30 patients with anterior chamber involvement, 15 were noted on initial examination and 15 during observation after therapy. Despite aggressive multimodality treatment, total response was never achieved and all eyes were eventually lost. Results of pathologic examination showed ciliary body invasion, which was held accountable for the poor response to therapy. Anterior chamber retinoblastoma is a poor prognostic sign which cannot be controlled effectively with current techniques and should be considered an indication for enucleation without delay.

Child↗

Macromolecular structure of axonal membrane during acute experimental allergic encephalomyelitis in rat and guinea pig spinal cord.

Axonal membrane structure during acute experimental allergic encephalomyelitis (EAE) was examined with freeze-fracture electron microscopy. Axons without myelin sheaths were prevalent within EAE spinal cords. Often these axons were associated with astrocytic processes, though membrane specializations were not observed at these sites. The demyelinated axons exhibited a highly asymmetrical partitioning of intramembranous particles (IMP), with approximately 2,000 particles/micron2 on P-faces and approximately 150/micron2 on E-faces. This distribution and density of IMP is similar to myelinated internodal membrane. The IMP were generally randomly distributed along the axons. However, in some regions, E-faces of demyelinated axons without paranodal-like membrane specialization in the vicinity displayed a greater than normal (approximately 500/micron2) particle density. Many of the IMP in these regions of increased density were of a large (greater than 10 nm) diameter. Axonal membrane bounded by a single set of paranodal oligodendroglial loops ('heminodal') was also observed, and the axolemma adjacent to the terminal glial loop exhibited a gradient of morphologies. The E-faces of presumed heminodal membrane most often displayed a moderately low density of IMP. However, in several instances, heminodal membrane exhibited a moderately high IMP density (approximately 1,100/micron2), similar to that observed within normal nodal membrane. In all cases, a high percentage of the E-face IMP within heminodal membrane were large. The results demonstrate that acute demyelination is associated with a maintenance of the integrity of certain components of the axolemma and an apparent dedifferentiation in other constituents.

Animals↗

Ploidy, proliferative activity, cluster differentiation antigen expression and clinical remission in high-grade non-Hodgkin's lymphoma.

Using a large range of monoclonal antibodies to specific cluster differentiation antigens the phenotypes of a series of high-grade non-Hodgkin's lymphomas of B- and T-cell type were investigated. Cell ploidy and proliferative fraction were assessed by fluorescent staining of DNA and flow cytometry and data on the incidence of complete clinical remission were obtained. With the exception of some lymphoblastic lymphomas, high-grade B-cell lymphomas normally expressed the pan B-cell antigens CD19 and CD22 but only immunoblastic lymphomas consistently expressed the pan B marker CD20. Variable, generally weak expression of CD21 was observed whilst CD23 expression was most prevalent in rapidly proliferative cases and in Burkitt's and centroblastic lymphomas. A rapidly proliferative, multilobated B-cell lymphoma displayed phenotypic properties intermediate between centroblastic and immunoblastic lymphomas. The T-cell lymphomas generally showed low proliferative activity and expression of CD4 prevailed over CD8. Most cases also showed CD2 and CD5 positivity with some also showing CD3 and CD7 expression. Patients with rapidly proliferative diploid or DNA aneuploid tumours obtained complete remission more readily than patients with lowly proliferative diploid tumours. An excess of early deaths occurred among T-cell cases.

Adolescent↗