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M M Smith

Publications and source records attributed to M M Smith.

At least 199 records · Page 11Linked to original sources

The simplified HF E-800 audiometer: calibration and normative aspects.

Although numerous viable applications of high frequency (HF) audiometry have been demonstrated in the past 20 yrs, a set of specifications analogous to those for diagnostic pure-tone audiometers (ANSI, 1969) is lacking. Thus, meaningful interpretation of HF thresholds must consider the system employed to assess auditory sensitivity. A cost-effective HF audiometer has recently been described based on the Grason-Stadler E-800 Bekesy audiometer in the fixed-frequency mode. Preliminary results indicate highly acceptable reliability and validity of thresholds. In the present study, 20 men and 65 women, all normally hearing young adults (170 ears) presenting with negative otoaudiologic histories produced HF ac thresholds from 8-20 kc/s. Excursion widths of pen tracings compared favorably with those of earlier reports in HF audiometer studies. The composite function (both sexes, both ears) was flat through 12 kc/s, with progressively greater SPLs required for higher frequencies. Neither gender nor ear-related differences were seen. Calibration was performed using the NBS 9 A 6-cc coupler and the manufacturer's flat-plate coupler for the Koss HV/X stereophone used. Conversion factors were presented so that either coupler could be used. A threshold function was recommended for use consisting of the composite median function for 170 ears. It was concluded that the Simplified HF E-800, or an analogous unit, could be used as a viable clinical tool, surpassing the cost effectiveness of a number of different HF audiometric systems.

Adolescent↗

Muscarinic cholinergic receptor-mediated attenuation of adenylate cyclase activity in rat heart membranes.

The regulation of adenylate cyclase by muscarinic cholinergic receptors has been studied in rat heart membranes. In the presence of isoproterenol the K0.5 for Mg2+-mediated activation of adenylate cyclase was 0.1 mM; the addition of the muscarinic receptor agonist oxotremorine increased the K0.5 for Mg2+, and activation by Mg2+ no longer followed mass action kinetics for a single site interaction. The extent of oxotremorine-mediated attenuation of adenylate cyclase exhibited a Mg2+ concentration dependence: in short-time assays at 0.25 mM free Mg2+ the attenuation of enzyme activity was 55 percent, whereas at 20mM Mg2+, only 20 percent inhibition was observed. The increase in the apparent K0.5 for Mg2+ in the presence of oxotremorine was less in 20 min assays than in 4 min assays. The effects of oxotremorine on the rates of activation and deactivation of adenylate cyclase also were examined. Oxotremorine increased the rate of deactivation of adenylate cyclase by two-fold. At low free Mg2+ concentrations, oxotremorine also decreased the rate of activation of adenylate cyclase in the presence of either 0.1 uM GTP gamma S or 1 uM GTP. An oxotremorine-mediated decrease in the rate of activation of adenylate cyclase activity was not detectable in the presence of greater than 3 mM Mg2+.

Adenylyl Cyclases↗

The pattern of histogenesis and growth of tooth plates in larval stages of extant lungfish.

Comparison of new data obtained in this study on Protopterus aethiopicus with that published on Protopterus aethiopicus and Neoceratodus forsteri has confirmed the suggestion that the pattern of histogenesis of tooth plates in the early larval stages is very similar in the two genera. These similarities are more apparent both when a common terminology is adopted, based on a topogenic classification, and when the fundamental assumption is made that a single morphogenetic system operates for all odontodes. The model to explain the structure of all vertebrate dentitions with separate teeth in single or multiple tooth rows has been found to apply to dipnoan dentitions with fused teeth in a composite tooth plate. In this model, the epithelial invagination surrounding the margins of the tooth plate represents the dental lamina and, where this is in contact with mesenchymal cells, cell clusters (protogerms) arise. From these protogerms new odontodes (teeth) may develop if factors to inhibit differentiation are not present. Sites for initiation of odontodes become restricted to the labial margins of existing ridges on the tooth plate. Experimental studies on mammalian tooth germs are discussed and a model proposed for control of odontogenesis and histogenesis in dipnoan dentitions. Patterns of growth of hypermineralised petrodentine have been analysed and shown to depend initially on the arrangement of odontodes, and subsequently upon the ability of special cells in the pulp to generate new and wider layers of petrodentine. The initial pattern of petrodentine depends upon the position of odontodes in the forming ridges of the tooth plate. Subsequent patterns of petrodentine depend upon the extent of replacement growth beneath the tritural surface. Specialised cells, petroblasts, secrete the petrodentine within a shell of dentine. These cells differentiate from cells of the dental papilla after odontoblasts have begun to form dentine. They are regarded as a unique type of cell for dipnoans.

Animals↗

Insulin action on glucose transport in cardiac muscle.

The mechanism of insulin action on glucose transport in rat hearts was studied. The glucose transport activity was determined after reconstitution into egg lecithin liposomes. Isolated rat hearts were perfused in the presence or absence of insulin and homogenized. The homogenate was fractionated by differential and sucrose density gradient centrifugations. Two subcellular fractions, designated as Fractions P-5 and P-6, contained glucose transport activity. Both fractions were enriched with 5'-nucleotidase (commonly known as a plasma membrane marker) and UDP-Gal:N-acetylglucosamine galactosyltransferase (known as a Golgi marker). However, only Fraction P-5 was concentrated with the insulin receptor and ouabain-sensitive p-nitrophenylphosphatase (both plasma membrane markers). The sedimentation properties of the glucose transport activity in Fraction P-6 were considerably different from those of galactosyltransferase. Insulin added to the heart before homogenization increased the glucose transport activity in Fraction P-5 approximately 1.6-fold while decreasing the activity in Fraction P-6 to approximately 62% of the control. These results are interpreted as follows. Both Fractions P-5 and P-6 are heterogeneous; nevertheless, Fraction P-5, but not Fraction P-6, may be enriched with the plasma membrane, which is assumed to be associated with glucose transport activity. Fraction P-6 may be concentrated with the Golgi apparatus; however, the latter may not be the structure (or vesicles) to which (intracellular) glucose transport activity is associated. Insulin appears to increase the glucose transport activity in rat hearts, at least in part, by inducing translocation of the glucose transport mechanism from the unidentified vesicles (in Fraction P-6) to the plasma membrane (in Fraction P-5).

Animals↗

Partial characterization of the glucose transport activity in the Golgi-rich fraction of fat cells.

The glucose transport activity solubilized from the basal and plus insulin forms of the Golgi-rich fraction of adipocytes was partially characterized, and the results were compared with those of the activity obtained from the plus insulin form of the plasma membrane-rich fraction. The transport activity was determined in a cell-free, reconstituted, system. Prior to reconstitution, the activities in the three preparations were all (a) stable at 0 degrees C for at least 4 h, but not at 37 degrees C or above; (b) most stable at pH 7-9, and (c) less stable in Tes than in Tris buffer. After reconstitution, the three activities were all (d) stable at 0 degrees C, (e) most active at pH 5.5, (f) mildly stimulated by divalent cations, (g) unaffected by insulin or 1 mM of several SH-blocking agents, (h) inhibited by heavy metal ions, 10-100 mM of monovalent salts, organic solvents, several sugar isomers, and specific sugar-transport inhibitors. The rates of D-glucose uptake by the three liposome preparations were all inhibited more strongly by 2-deoxy-D-glucose or 3-O-methyl-D-glucose than by D-glucose. These data indicate that the general properties of the glucose transport activity in the Golgi-rich fraction are similar to those of the activity in the plasma membrane-rich fraction.

Adipose Tissue↗

Effects of divalent cations on the regulation of insulin-sensitive glucose transport and cAMP phosphodiesterase in adipocytes. Insulin-like effects of divalent cations.

Effects of divalent cations on the regulation of glucose transport and cAMP phosphodiesterase in isolated rat epididymal adipocytes were studied. EDTA (5 mM) moderately inhibited the binding of insulin to adipocytes in Krebs-Henseleit Hepes buffer. In the same buffer, A-23187 (an ionophore specific for divalent cations; 50 microM) plus EDTA (5 mM) almost completely blocked the insulin- or hydrogen peroxide-dependent stimulation of phosphodiesterase. This inhibition was not secondary to the loss of ATP. When cells that had been treated with A-23187 plus EDTA were washed and then exposed to 1-10 mM of divalent cations, the cellular phosphodiesterase activity was elevated. Mn2+ was most stimulatory, Mg2+ was next, and Ca2+ was least effective. The stimulatory effects were enhanced by insulin. In the presence of insulin, Mn2+ at 10 mM was less stimulatory than that at 1 mM. In regular Krebs-Henseleit Hepes buffer, Mn2+ greatly stimulated phosphodiesterase if cells were first exposed to A-23187. The Mn2+-dependent stimulation was blocked by treatment of cells with 2,4-dinitrophenol. Results essentially parallel to those described above were also obtained when the rate of glucose transport was determined. The above results indicate that divalent cations mildly support the extracellular binding of insulin to its receptor, facilitate the physiological actions of insulin, and mimic the hormone actions, presumably by stimulating an intracellular enzyme.

2,4-Dinitrophenol↗

Operationalizing the concept of sexuality comfort: applications for sexuality educators.

Thirty-two high school and college educators participated in a study designed to operationalize the concept of sexuality comfort. Research questions asked were: "What is the nature of sexuality comfort?" and "Can the concept, of sexuality comfort be defined operationally?" An interview guide developed with input from an expert panel of health/sexuality educators and semanticists facilitated data collection. Data were categorized and tabulated through a systematic process. This coding process, performed by independent coders, yielded 97.2% reliability. Based on the results, an operational definition of sexuality comfort was delineated. Because an operational definition is one which tells what to do to experience the thing defined, the operational definition of sexuality comfort has immediate practical applications to preparation programs for prospective sexuality educators as well as those currently working in the field.

Attitude↗

High-frequency Békésy audiometry. V. Excursion width.

26 normally hearing young adults produced Békésy-type tracings for pure tones ranging from 7 to 19 kHz. Tones were pulsed (2.5/s) and delivered in the fixed-frequency mode. Chart rate (1 octave/min) and rate of attenuation (2.5 dB/s) were analogous to that typically used in clinical Békésy audiometry. Results indicated that subjects typically produced median excursion widths ranging from 5 to 15 dB. No systematic change in excursion width for conventional-frequency Békésy audiometry. The results of the present study were discussed regarding their utility in validation of responses to Békésy audiometry.

Acoustic Stimulation↗

Muscarinic cholinergic receptors of two cell lines that regulate cyclic AMP metabolism by different molecular mechanisms.

The attenuation of cyclic AMP accumulation occurs by different mechanisms in 1321N1 astrocytoma cells and NG108-15 neuroblastoma X glioma cells. In 1321N1 cells, cholinergic agonists reduce cyclic AMP accumulation through a Ca2+-dependent activation of phosphodiesterase; in NG108-15 cells, muscarinic receptor-mediated effects on cyclic AMP metabolism occur through inhibition of adenylate cyclase. The goal of the current study was to determine whether different pharmacological specificities were expressed by the muscarinic receptor populations of these two cell lines. The affinity of muscarinic receptors for [3H]quinuclidinyl benzilate (6 pM), [3H]N-methylscopolamine (50 pM), and atropine (80 pM) was similar in membrane preparations from each cell line. The affinity of the antagonist, pirenzepine, which has been proposed to be a selective ligand for a muscarinic receptor subtype, was 3-fold higher in competition binding assays carried out with membranes of 1321N1 cells, than with NG108-15 cells. The Hill coefficients of pirenzepine competition curves were not significantly different from unity in both cell lines. This selectivity of pirenzepine was also apparent in studies of the competitive inhibition of carbachol-induced attenuation of cyclic AMP accumulation in intact cells. Differences in the relative affinities of agonists were observed in competition binding analyses carried out with membranes in the presence of GTP and absence of Mg2+. The Ki values of bethanechol and carbachol were 5- and 12-fold lower for receptors of NG108-15 cells than those of 1321N1 cells and the Ki of methacholine was 3.5-fold lower for 1321N1 cells than for NG108-15 cells. The affinities of oxotremorine and arecoline were similar between the two cell lines. These differences in agonist affinities between the two cell lines were much smaller in analyses of muscarinic receptor-mediated effects on cyclic AMP metabolism in intact cells. Taken together, these data suggest that muscarinic receptors of differing pharmacological specificities regulate cyclic AMP metabolism by different mechanisms in 1321N1 and NG108-15 cells.

Animals↗

Modification of receptor-mediated inhibition of adenylate cyclase in NG108-15 neuroblastoma X glioma cells by n-ethylmaleimide.

Previous studies with membranes from rat heart (Mol. Pharmacol. 21: 570-580, 1982) and human platelets (J. Biol. Chem. 257: 2829-2833, 1982) have suggested that inhibition of adenylate cyclase by occupation of hormone receptors is blocked by pretreatment of membranes with relatively low concentrations of N-ethylmaleimide (NEM). Using membranes derived from NG108-15 neuroblastoma X glioma cells as a model system, we have examined the effect of NEM on the interaction of three inhibitory receptors with adenylate cyclase. Pretreatment of membranes with 100 to 216 microM NEM resulted in a loss of the capacity of agonists to inhibit adenylate cyclase through muscarinic cholinergic and opiate receptors and a loss of GTP-sensitive high-affinity binding of agonists to both of these receptors. Under the same conditions, stimulation of adenylate cyclase by prostaglandin E1 was unchanged. In contrast to the total loss of capacity to inhibit adenylate cyclase by muscarinic and opiate receptor activation, the inhibition of adenylate cyclase by activation of alpha-2 adrenergic receptors was only partially blocked by maximally effective concentrations of NEM. Similarly, GTP-sensitive high-affinity binding of epinephrine to alpha-2 receptors still occurred in NEM (316 microM)-treated membranes. Whereas only a decrease in the efficacy of muscarinic and opiate receptor agonists for inhibition of adenylate cyclase occurred as a result of NEM treatment, pretreatment of membranes with 316 microM NEM resulted in a 30-fold decrease in the potency of epinephrine for inhibition of adenylate cyclase.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclase Inhibitors↗

Combination of immunocytochemistry and radioligand receptor assay to identify beta-adrenergic receptor subtypes on astroglia in vitro.

There is an increasing need to assess the distribution of receptors for neuroactive substances on specific neural cell types. This study describes the establishment of methodology that combines the quantification of beta-adrenergic receptor subtypes by radioligand binding assays with immunocytochemical analysis of the contribution of astroglia (identified by the presence of glial fibrillary acidic protein) and fibroblasts (identified by the presence of fibronectin) to cultures prepared from neonatal rat cerebral cortex. The effects of subtle changes in culture methodology on the cellular composition of cerebral cortical cultures and the distribution of beta-adrenergic receptor subtypes were examined. The data indicate that (1) a decrease in the density of the initial plating suspension, (2) an increase in the age of the animals, or (3) supplementation of the cortical cell suspension with meningeal fibroblasts all result in an increase in fibronectin staining and a decrease in glial fibrillary acidic protein antibody staining. This change in the cellular composition of the cortical cultures correlated with an increase in the number of beta 2-adrenergic receptors and a corresponding decrease in the number of beta 1-adrenergic receptors. These observations point out the care which must be exercised when preparing primary astroglial cultures of sufficient purity for large-scale biochemical and pharmacological studies.

Animals↗

Modulation of muscarinic cholinergic receptor affinity for antagonists in rat heart.

Modulation of the affinity of agonists and antagonists at muscarinic cholinergic receptors in rat heart membranes was investigated using the radiolabeled antagonist, [3H]quinuclidinyl benzilate ([3H]QNB), and the radiolabeled agonist, [methyl-3H]oxotremorine acetate ([3H]OXO). Receptor affinity for oxotremorine measured in competition binding assays with [3H]QNB or by equilibrium binding of [3H]OXO was increased when the incubation temperature was reduced to 4 degrees C. In contrast, the receptor affinity for [3H]QNB was decreased at lower incubation temperatures and a marked effect of guanine nucleotides on the affinity for [3H]QNB was revealed. Guanine nucleotides increased receptor affinity for [3H]QNB without changing the total number of binding sites. The GTP-induced increase in the affinity for [3H]QNB was reflected by an increase in the rate constant for association of [3H]QNB. At subsaturating ligand concentrations, guanine nucleotides increased [3H]QNB binding and decreased [3H]OXO binding with the same order of potency: GppNHp = GTP gamma S greater than GTP greater than guanosine 5'-diphosphate greater than GMP. Free Mg++ ion was required to observe guanine nucleotide effects on antagonist binding. Pretreatment of heart membranes with N-ethyl-maleimide increased [3H]QNB affinity and blocked the effects of guanine nucleotides. N-Ethylmaleimide also decreased [3H]OXO binding and increased [3H]QNB binding with a similar concentration-effect relationship. Thus, antagonist and agonist binding to muscarinic cholinergic receptors is modulated in a reciprocal manner by a number of factors; this modulation appears to reflect interaction of agonist and antagonist-occupied receptors with a guanine nucleotide regulatory protein, Ni.

Animals↗

Yeast H3 and H4 histone messenger RNAs are transcribed from two non-allelic gene sets.

The genes coding for the H3 and H4 histones of Saccharomyces cerevisiae have been isolated by recombinant DNA cloning. The genes were detected in a bacteriophage lambda library of the yeast genome by hybridization with plasmids containing the cloned Psammechinus miliaris sea urchin histone genes (pCH7) and the cloned Drosophila histone genes (cDM500). Two non-allelic sets of the H3 and H4 genes have been isolated. Each set consists of one H3 gene and one H4 gene arranged as a divergently transcribed pair separated by an intergene spacer DNA. The histone genes were located on the cloned yeast fragments by S1 nuclease mapping, as was a gene (SMT1) of unknown function that does not code for a histone but is closely linked to one of the histone sets. Sequence homology between the two non-allelic sets is confined to the coding regions of the respective genes while the flanking DNA and intergene spacer DNA are extensively divergent. Cellular RNA homologous to the histone genes, including transcribed non-coding sequences unique to each of the four genes, was detected by S1 mapping, thus demonstrating that all four genes are transcribed in vegetative cells.

Base Sequence↗

DNA sequences of yeast H3 and H4 histone genes from two non-allelic gene sets encode identical H3 and H4 proteins.

The complete DNA sequences of two loci encoding H3 and H4 histones in Saccharomyces cerevisiae have been determined. Each locus contains one H3 and one H4 gene. The genes at each locus are divergently transcribed and the coding sequences are separated by 646 base-pairs at one locus and 676 base-pairs at the other. The H3 genes code for identical histone H3 proteins and the H4 genes code for identical histone H4 proteins. The yeast proteins differ from histones H3 and H4 of calf by 15 and 8 amino acid substitutions, respectively, and these differences are largely confined to the carboxy-terminal halves of the proteins. The genes demonstrate a bias in synonymous codon usage similar to that noted for other yeast genes. This bias is confined to the coding sequences of the genes and is specific for the reading frame encoding the proteins. The coding sequence of each gene is flanked on both sides by DNA with an A + T content of 70 to 80%. Possible regulatory sequences are located relative to the 5' and 3'-termini of the histone H3 and H4 RNA transcripts.

Base Sequence↗

Connections of the mesencephalic locomotor region (MLR) I. Substantia nigra afferents.

These studies were designed to determine whether or not substantia nigra (SN) neurons project to the mesencephalic locomotor region (MLR). An attempt was made to activate SN neurons antidromically from the same site which induced locomotion on a treadmill following a precollicular-postmammillary transection in the same animal. Less than 10% of posterior SN neurons were activated antidromically from the physiologically-identified MLR. These results support previous anatomical findings describing a sparse projection from the SN to the MLR [5]. Locomotion on a treadmill was elicited at low current strengths (20-50 muA) from an area around the cuneiform nucleus in the posterior mesencephalon. This area included the lateral central gray, mesencephalic trigeminal root, dorsal brachium conjunctivum and nucleus tegmenti pedunculopontinus (NTPP) and perhaps anterodorsal locus coeruleus. Stimulation of the area just described induced a complete stepping cycle with a flexion phase and a three-part extension phase. Stimulation of the posterior SN produced spastic locomotion on a treadmill at higher current strengths (70 muA) in cats with a precollicular-postmammillary transection.

Afferent Pathways↗

Career development in nursing: an individual and professional responsibility.

Nursing with its variety of career options has much to offer individuals who can capitalize on their skills, growth potential, and professional opportunities through planned career development. More needs to be done, however; as Lysaught observes, "Nursing is the only profession that has no career path related to the intrinsic reason that brought people to the profession in the first place." Working together, nursing service and education must prepare nurses who view nursing as a career and not just as a series of jobs, rewarding nurses for direct patient care services, addressing professional issues that will assist nurses in their career development, providing opportunities for career planning, and "finding ways to share with prospective nurses the excitement and challenge of nursing".

Career Choice↗