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Biomedical subjects

M E Smith

Publications and source records attributed to M E Smith.

At least 307 records · Page 17Linked to original sources

Stimulated release of phosphatidylinositol phosphodiesterase in an isolated phrenic nerve-diaphragm preparation.

Electrical stimulation of the phrenic nerve in an isolated nerve-diaphragm preparation resulted in the release of phosphatidylinositol phosphodiesterase into the organ bath. The released enzyme was Ca2+-dependent and exhibited two pH optima. The enzyme was released in response to nerve stimulation even in the presence of d-tubocurarine in concentrations that block neuromuscular transmission, and was not therefore released from the muscle as a consequence of its contractile activity. Phosphatidylinositol phosphodiesterase activity was determined in the soluble cytosol fractions prepared from different regions of skeletal muscles and from normal peripheral nerves and nerves that were degenerating after transection. The specific activity of the enzyme in the cytosol from the endplate-rich region of the diaphragm was significantly greater than that in cytosol from either the endplate-free region of the diaphragm or from the phrenic nerve. In degenerating nerve the activity of the enzyme was greater in the distal stump than in the proximal stump at 36 h after nerve section. Possible roles for released phosphatidylinositol phosphodiesterase at the neuromuscular junction are discussed.

Animals↗

Effects of diacylglycerol and phorbol ester on acetylcholine release and action at the neuromuscular junction in mice.

Miniature endplate potentials and nerve-evoked endplate potentials were studied in a phrenic nerve-diaphragm preparation of the mouse. A phorbol ester, phorbol-12 beta, 13 alpha-dibutyrate, and a diacylglycerol, 1-oleyl-2-acetyl-sn-glycerol, both increased the frequency of miniature endplate potentials. The effect of the phorbol ester on the frequency was still significant when the preparation was incubated in a calcium-deficient solution. The phorbol ester, but not the diacylglycerol, caused a significant increase in the amplitude of the miniature potentials. The phorbol ester also increased the amplitude of the endplate potentials in the presence of (+)-tubocurarine. The mechanisms of action of phorbol ester and diacylglycerol are discussed in relation to the control of acetylcholine release and action at the neuromuscular junction.

Animals↗

Major histocompatibility complex class II antigen expression in B and T cell non-Hodgkin's lymphoma.

An immunohistochemical study of 46 B and T cell non-Hodgkin's lymphomas, using monoclonal antibodies to the products of the major histocompatibility complex (MHC) class II antigen subregions, DP, DQ, and DR, showed that most B and T cell lymphomas express these antigens. Both coordinate and non-coordinate expression of MHC class II antigens was observed, but this did not correlate with immunological phenotype, morphological grade, or proliferation index as determined by flow cytometry.

B-Lymphocytes↗

Binding of quinine- and quinidine-dependent drug antibodies to platelets is mediated by the Fab domain of the immunoglobulin G and is not Fc dependent.

The antibody domain controlling reactions between platelet membranes and drug-dependent (dd) antibodies from patients with thrombocytopenia induced by cinchona alkaloids was studied using F(ab')2, Fab, and Fc fragments made from purified dd-IgG. By direct binding radioimmunoassay (RIA) measurements, 20,000 to 50,000 antibody molecules bound per platelet equivalent of purified platelet membranes at apparent saturation with three different antibodies. F(ab')2 and Fab fragments bound to platelet membranes drug dependently but Fc fragments did not. The ability of dd-IgG fragments to compete with intact IgG was quantitatively measured by RIA and by complement fixation. F(ab')2 and Fab competed with intact IgG at an 8:1 and greater than 50:1 molar ratio, respectively, in RIA, and at a 1.6-3:1 and 44-75:1 ratio, respectively, by complement fixation assays. Fc did not compete with IgG in either assay. We conclude that the Fab domain supports attachment of dd antibody to the platelet surface.

Autoantibodies↗

Border disease. Virus-induced decrease in thyroid hormone levels with associated hypomyelination.

Border disease (BD) was induced in lambs by inoculation of their dams at 50 days gestation with Border disease virus (BDV) isolate #31. At birth, the clinically affected lambs had diffuse spinal cord hypomyelination, confirmed by immunocytochemical staining for myelin-associated glycoprotein and myelin basic protein. In the BD lambs, large numbers of thyroid follicular epithelial cells and scattered pituitary cells contained BDV antigen by immunofluorescence staining. Double labeling techniques demonstrated the BDV-infected pituitary cells to contain growth hormone, adrenocorticotrophic hormone, prolactin, or luteinizing hormone. Cells containing thyroid stimulating hormone were rare and were not positive for BDV antigen. Infection of the pituitaries and thyroid glands caused no detectable morphologic changes as compared to controls. The BD lambs had statistically significantly (p less than 0.05) lower mean serum concentrations of thyroxine and L-3,3',5-triiodothyronine as compared to age-matched uninfected controls. Similar significant differences in the mean plasma levels of growth hormone and thyroid stimulating hormone were not found. In addition, the BD lambs had a statistically significant (p less than 0.05) lower mean activity of the myelin-associated, thyroid hormone dependent enzyme, 2',3'-cyclic nucleotide-3'-phosphodiesterase in spinal cord tissue. Although not conclusive, these results indicate that the hypomyelination in BD may be due to depressed levels of circulating thyroid gland hormones secondary to a noninflammatory and noncytolytic infection of the thyroid gland by BDV. This is one of the first reports indicating that a virus-induced hormonal alteration may cause a congenital lesion in animals.

Animals↗

Cognitive evoked potentials as modulatory processes in human memory formation and retrieval.

The complex experiential nature of human cognitive memories implies that their formation and retrieval result from neural activity that is widespread and patterned. This integration of widespread activity into coherently patterned gestalts is accompanied by event related brain potentials (ERPs). ERP component N4, reflecting associative activation, declines as words or faces become more familiar. ERP component P3, reflecting cognitive closure, generally grows larger with familiarity. Similar changes in the N4/P3 are seen to familiarity in remote semantic memory. The N4/P3 may be generated directly by the multitude of specific neuronal interactions that constitute associative activation and contextual closure. Alternatively, the N4/P3 may be generated by diffuse modulatory pathways exerting non-specific control over these same interactions. In any case, the N4 and P3 appear to be generated simultaneously in several neocortical and subcortical structures, including the medial temporal lobe (MTL), where lesions are known to produce a profound deficit in learning new cognitive material. The MTL in the dominant hemisphere is necessary for the extratemporal N4/P3 generators to alter their response to words that are familiar in context. The mechanism whereby the MTL controls cortical activation is unknown. However, some hippocampal neurons are activated by particular words, suggesting that the MTL contributes specific information to the cortex during memory retrieval. These properties of the N4/P3 bear a close similarity to modulatory processes which have been found to aid formal associative networks in creating patterns that best represent current input in light of past experience. These modulatory processes consist of an initial generalized activation that encourages partially specified widespread elements to emerge as a network, followed by inhibition that focuses the emerging pattern into a coherent gestalt.

Brain↗

Alterations in plasma lipoproteins and apolipoproteins in experimental allergic encephalomyelitis.

Plasma lipoproteins were investigated during the active clinical phase of experimental allergic encephalomyelitis (EAE), a demyelinating disease of the central nervous system. Three groups of Lewis rats were compared: untreated controls, Freund's adjuvant-treated controls (FAC), and rats receiving one injection of myelin in Freund's adjuvant. After onset of clinical symptoms, 12 and 16 days after injection, there were higher concentrations of cholesterol and low and high density lipoproteins (LDL and HDL) in EAE plasma. The increase was due to apoE-containing HDL1 and HDL, according to density, particle size, and apolipoprotein compositions of isolated lipoproteins and immunoblots of whole plasmas after gradient gel electrophoresis. In EAE, the cholesterol-to-apoprotein ratio was increased and the low density lipoprotein distribution profile was shifted toward lower density. The Freund's adjuvant-treated control rats showed some changes qualitatively similar to those of EAE, albeit far smaller in magnitude. Changes in LDL in EAE might be related in part to lowered plasma very low density lipoproteins (VLDL); however, weight loss in control animals did not increase plasma cholesterol or apoE relative to apoA-I. Lesions in the central nervous system and/or activation of macrophages might be causally related to the large increase in plasma apoE. The major changes in apoE-containing lipoproteins are undoubtedly significant for the altered immune function in EAE.

Animals↗

Magnetic resonance imaging in choroidal tumors.

Magnetic resonance imaging (MRI) was performed on 13 patients with choroidal tumors to determine whether this technique could detect and portray an intraocular tumor and to investigate additional biochemical parameters of the diseased tissue. In 11 of 13 patients, the lesion was depicted, and its gross morphology was outlined with a clarity approaching that of computed tomography. We were able to apply principles derived from MRI studies in other portions of the body and identify trends in the characterization of lesions of different etiologies. The relative T1 and T2 values for each of the major pathologic categories (malignant melanoma, metastatic carcinoma, and benign choroidal lesions) are presented and discussed. In addition, MRI was clearly superior to other techniques in the detection and delineation of associated intracranial lesions.

Choroid Neoplasms↗

Effect of phospholipase C on the binding of alpha-bungarotoxin to isolated plasma membranes of rat skeletal muscle.

Sarcolemmal membranes were isolated from hindlimb muscles of the rat and the specific binding of [125I]alpha-bungarotoxin to the membranes was determined. Incubation of the membranes with a purified preparation of phospholipase C (ex Clostridium perfringens) increased the specific binding of the toxin (Bmax). The apparent dissociation constant (Kd) for the binding was unchanged by treatment with the enzyme. The possibility that latent acetylcholine receptors exist in muscle sarcolemma, and that these receptors can be activated by the enzyme, is discussed.

Acetylcholine↗

Ultrasonic hyperthermia and radiation in the management of intraocular malignant melanoma.

Hyperthermia and radiation were used in combination to treat four patients with choroidal malignant melanoma. This technique uses ultrasonically induced hyperthermia synergistically with radiation to destroy tumor cells. The lower levels of radiation used should avoid the late vascular and inflammatory complications seen in conventional radiation therapy. Tumors were scanned by a computerized diagnostic ultrasound system before treatment and assigned an acoustic tissue type on the basis of a statistical comparison of their ultrasound backscatter spectrum with spectra of tumors of known pathologic status. During the follow-up period, the longest of which was 15 months, all tumors demonstrated regression patterns consistent with choroidal tumors of the same acoustic tissue types treated with conventional radiation therapy.

Aged↗

Comparison of MMPI clinical scale and critical item changes of adult outpatients and parents of child psychiatry outpatients during the 1970s.

The present investigation is a replication of the Holmes, Sabalis, Chestnut, and Khoury (1984) study of MMPI critical item endorsement changes and MMPI clinical scale shifts in the parents of children seen at the William S. Hall Psychiatric Institute, Columbia, South Carolina during the 1970s. The current study evaluates MMPIs (N = 749) of adult, female, and male psychiatric outpatients seen during the 1970s. The general MMPI changes observed in the adult psychiatric outpatient population were not similar to those changes seen in the parent population. However, an important specific change on the Masculine/Feminine Scale for the adult outpatients was discussed.

Adult↗

Cluster differentiation antigen expression, proliferative activity and clinical stage in centroblastic centrocytic lymphomas.

Using a panel of B-cell antibodies recognizing clusters of leucocyte differentiation antigens, immunostaining patterns of eight reactive lymph nodes and 28 centroblastic/centrocytic and centrocytic lymphomas have been studied. Centroblastic/centrocytic and centrocytic lymphomas retained many of the B-cell differentiation antigens and neoplastic follicles partially recapitulated the staining patterns observed in reactive follicles. Centrocytic lymphomas usually expressed a heavy chain mantle zone-like phenotype. Nearly one-half of follicular lymphomas showed extension of neoplastic cells into interfollicular areas as evidenced by positivity for CD10 (common acute lymphoblastic leukaemia) and/or CD9 (immature B-cell) and CD23 (B-blast cell) antigens. Cases showing interfollicular involvement also manifested considerable phenotypic heterogeneity. Light chain restriction could not be used to determine interfollicular involvement because of the presence of many non-neoplastic cells. Most follicular lymphomas retained a polyclonal mantle around at least some neoplastic follicles and in no case was a monoclonal mantle seen. Most lymphomas (16/21) were diploid when examined by flow cytometry. Diploid tumours exhibiting interfollicular lymphomatous involvement had high proliferation (S + G2) fractions and these lymph nodes were usually derived from patients with widespread disease. Tumours containing a high percentage of cells in the G0/G1 phases displayed fewer B-cell differentiation antigens than tumours with low G0/G1 fractions.

Antigens, Neoplasm↗

The role of phospholipases from inflammatory macrophages in demyelination.

Activated macrophages harvested from rat peritoneum were shown to contain phospholipase A1, A2 and lysophospholipase activities which were defined on a series of radiolabelled phospholipid substrates. During in vitro culture of these elicited macrophage populations, phospholipase enzymes were secreted into the culture medium. Radiolabelled myelin, prepared from young rats after intracerebral injection of 14C acetate, was used as a substrate to analyze the susceptibility of central nervous system (CNS) myelin to attack by cell-associated and secreted macrophage enzymes. Homogenates of peritoneal macrophages degraded the myelin lipids at acid pH; phosphatidyl choline (PC) and ethanolamine phosphatide (EP) were both degraded with liberation of free fatty acid and small amounts of lysolipids. The ethanolamine lipids were most vulnerable; up to 20% of this fraction was degraded in six hours. Selected batches of macrophage culture supernatant similarly degraded the myelin EP at acid pH. These results suggest that phospholipase enzymes, released from activated macrophages in close proximity to the myelin sheath, may participate in primary demyelination in inflammatory CNS lesions.

Animals↗

Human medial temporal lobe potentials evoked in memory and language tasks.

Lesion evidence indicates that the human medial temporal lobe (MTL) makes an important contribution to Recent Memory formation and retrieval very soon after a stimulus item is encountered. For verbal materials, this contribution is lateralized to the language dominant hemisphere. Evoked potentials recorded from the MTL during verbal recognition memory display two late endogenous components. Both show differences between repeated target words and non-repeated distractor words. The first component is usually negative and has an average latency of 460 msec. It is also observed in lexical decision and picture naming tasks. This component is similar in latency, morphology, and task correlates to the scalp-recorded N4 potential. This 'MTL-N4' is smaller in amplitude to words recognized as repeats and is largest in amplitude in the left MTL. The second component is usually positive and has an average latency of 620 msec. It is similar in morphology and MTL topography to the P3-like component evoked at 360 msec to rare tones in auditory discrimination tasks. This 'MTL-P3' is larger in amplitude to words recognized as repeats. Both components are of very large amplitude and invert polarity over short distances within the MTL. Hence, they appear to be locally generated in the MTL. The extent to which volume conduction of these MTL potentials contribute to scalp-recorded EPs is unclear. The MTL-N4 might be involved with memory formation and retrieval processes, and the MTL-P3 might index completion of the detection-recognition cycle.

Adult↗

Critique of Miller's "degree of lateralization as a hierarchy of manual and cognitive skill levels".

Miller (Neuropsychologia 20, 155-162, 1982) reported a correlational study in which an association between handedness measures and tests of cognitive development was found. It was concluded that the degree to which manual dexterity is lateralized predicts cognitive development, and that these measures are related aspects of the development of cerebral specialization. This conclusion is questionable in that the intellectual skills necessary for performance on the cognitive development tests are probably not functionally lateralized. In addition, when the influence of chronological age is partialled out, there is no residual correlation between lateralization of manual dexterity and cognitive performance.

Child↗