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Biomedical subjects

M Myers

Publications and source records attributed to M Myers.

At least 109 records · Page 6Linked to original sources

The fractional distribution of the cardiac output in man using microspheres labelled with technetium 99m.

To investigate the distribution of organ blood flow in patients we have developed a method of quantitating the whole-body fractional distribution of 99Tcm-labelled microspheres. The microspheres were injected into the left ventricle in nine patients with normal cardiac indices (greater than 3 1/min/m2; Group A) and 11 patients with low cardiac indices (less than 2.51 l/min/m2; Group B). The fractional organ content of the total injected dose was estimated following correction for geometry and transmission using a gamma camera. Cerebral blood flow was 579 +/- 163 ml/min (mean +/- SD) in Group A and 593 +/- 158 ml/min in Group B (p not significant (NS)). Myocardial flow in Group A was 266 +/- 82 ml/min and in Group B was 237 +/- 57 ml/min (p, NS). Total renal blood flow was 749 +/- 161 ml/min in Group A and 614 +/- 181 ml/min in Group B (p less than 0.01). There was a negative correlation between cardiac index and the percentage of the cardiac output distributed to brain (r = -0.70, p less than 0.01), heart (r = -0.67, p less than 0.01) and kidneys (r = -0.47), p less than 0.05). Low output cardiac failure is, therefore, associated with relative preservation of cerebral and myocardial blood flow and, to a lesser extent, of renal flow. A similar technique using dual labelling would allow an accurate estimation in individual patients, of the change in organ blood flow associated with transient alterations in cardiac output states.

Adult↗

Calorimetric and fluorescence characterization of interactions between enkephalins and liposomal and synaptic plasma membranes containing gangliosides.

The interactions of the opioid peptide [D-Ala2]methionine-enkephalinamide with dipalmitoylphosphatidylcholine (DPPC) large unilamellar vesicles containing gangliosides GM1, Gd1a, and Gt1b and synaptic plasma membranes selectively enriched with dimyristoylphosphatidylcholine (DMPC) and ganglioside Gd1a have been investigated by using high-sensitivity differential scanning calorimetry. In the absence of gangliosides, the addition of enkephalinamide in concentrations of up to 10(-3) M does not induce any appreciable change in the heat capacity function of DPPC. In the presence of gangliosides, however, changes in the heat capacity function were observed with as little as micromolar concentrations of the enkephalinamide; the same is true for DMPC-Gd1a-enriched synaptic membranes. The magnitude and the nature of the enkephalinamide effect depend on the type of ganglioside studied. For DPPC vesicles containing ganglioside GM1 only a slight broadening in the heat capacity function and a small upward shift in the transition temperature were observed. For DPPC vesicles containing ganglioside Gd1a the effect was more dramatic; enkephalinamide concentrations as low as 10(-5) M caused the appearance of two well-defined peaks in the heat capacity function in contrast to the one peak observed in the absence of enkephalinamide. In the case of DPPC vesicles containing ganglioside Gt1b the enkephalinamide effect was seen at concentrations of 10(-4) M or higher. Synaptic plasma membranes were isolated from bovine brain, selectively enriched with exogenous lipid, and their thermotropic behavior was characterized by steady-state fluorescence spectroscopy and differential scanning calorimetry. This lipid enrichment results in the appearance of a membrane phase transition otherwise absent in the intact membrane preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Alpha-adrenoreceptor reagents. 3. Synthesis of some 2-substituted 1,4-benzodioxans as selective presynaptic alpha 2-adrenoreceptor antagonists.

The synthesis and pharmacological activity of a series of 2-substituted derivatives of the selective alpha 2-adrenoreceptor antagonist idazoxan (RX 781094) is described. Substitution in this position by alkyl, alkenyl, cycloalkenyl, and alkoxy groups in many cases gives compounds whose potencies and selectivities are significantly greater than those of the parent compound.

Adrenergic alpha-Antagonists↗

Cis-platinum, doxorubicin, and methotrexate treatment for recurrent cervical cancer.

A combination of cis-platinum, doxorubicin (Adriamycin), and methotrexate was used to treat 28 patients with recurrent cervical cancer. Seven patients achieved a partial response with a median duration of ten months. Two patients achieved a complete response with a median duration of 14 months. The overall response rate was 32%. Ten patients with stable disease had a median progression-free interval of 4.5 months. Toxicity was acceptable.

Adenocarcinoma↗

Modulation of neuraminidase activity by the physical state of phospholipid bilayers containing gangliosides Gd1a and Gt1b.

The thermotropic behavior of large unilamellar dipalmitoylphosphatidylcholine vesicles containing the disialoganglioside Gd1a and the trisialoganglioside Gt1b on their outer surface has been studied as a function of the ganglioside molar fraction and Ca2+ concentration by using high-sensitivity differential scanning calorimetry and steady-state fluorescence spectroscopy. These studies indicate that both gangliosides have an ordering effect on the hydrocarbon region of the bilayer and that this effect is enhanced by the presence of Ca2+ ions. The calorimetric experiments also indicate that ganglioside Gt1b has an intrinsic tendency to phase separate into compositional-rich ganglioside domains even in the absence of Ca2+. Ganglioside Gd1a, on the other hand, only phase separates at Ca2+ concentrations equal to or higher than 10 mM. These studies have allowed us to identify and evaluate the factors affecting the rates of hydrolysis of gangliosides by the soluble neuraminidase from Clostridium perfringens. The data presented in this paper indicate that the rates of hydrolysis of membrane-bound gangliosides are correlated to the physical state of the membrane and the state of aggregation of the ganglioside molecules within the lipid bilayer. For membrane-bound gangliosides, maximal activation energies were found at temperatures slightly below the lipid phase transition temperature. The rates of hydrolysis of the soluble substrate sialyllactose or that of the micellar ganglioside is independent of Ca2+ concentration, whereas the rates of hydrolysis of membrane-bound ganglioside are inhibited by Ca2+ especially under conditions in which the clustering effect of Ca2+ is maximal. These studies suggest that the soluble neuraminidases from Clostridium perfringens prefer ganglioside substrates that are dispersed within the membrane and not forming part of largely aggregated clusters.

Calcium↗

Alpha-adrenoreceptor reagents. 2. Effects of modification of the 1,4-benzodioxan ring system on alpha-adrenoreceptor activity.

Modification of the 1,4-benzodioxan ring present in RX 781094 has not previously been considered. This paper describes a number of analogues of this ring system, including compounds in which one of the oxygen atoms has been replaced by a methylene group and also those in which the ring size has been changed to give, for example, furan and thiophene derivatives. The dihydrobenzofuranylimidazoline compound 7 is the only analogue possessing presynaptic antagonist potency potency and selectivity comparable to that of 1. In view of this result, a number of derivatives was prepared to determine the structure-activity relationships within this series. Many derivatives, as well as the parent compound 7, were found to possess presynaptic alpha 2-adrenoreceptor antagonist and postsynaptic alpha 1-adrenoreceptor partial agonist properties. Two of the selective presynaptic antagonists, 13 and 14 possess greater potency and selectivity than that possessed by 1. The 5-chloro derivative 25 is twice as potent as after oral administration but only about half as potent when given intravenously.

Adrenergic alpha-Antagonists↗

Infants' discrimination of the duration of a rapid spectrum change in nonspeech signals.

Two-month-old infants discriminated complex sinusoidal patterns that varied in the duration of their initial frequency transitions. Discrimination of these nonspeech sinusoidal patterns was a function of both the duration of the transitions and the total duration of the stimulus pattern. This contextual effect was observed even though the information specifying stimulus duration occurred after the transitional information. These findings parallel those observed with infants for perception of synthetic speech stimuli. Specialized speech processing capacities are thus not required to account for infants' sensitivity to contextual effects in acoustic signals, whether speech or nonspeech.

Humans↗

Induction of tissue transglutaminase in mouse peritoneal macrophages.

Tissue transglutaminase accumulates rapidly and to very high levels (1-2% of cellular protein) in mouse peritoneal macrophages cultured in mouse serum. The induction is due to accelerated synthesis of the enzyme (150-fold increase) that occurs within 90 min of exposure of the cells to a heat-labile constituent of serum or plasma. The induction is reversible and is not reproduced by known activators of macrophage function such as lipopolysaccharide, muramyl dipeptide, and tuftsin. In animals, elevated levels of tissue transglutaminase are also found in inflammatory macrophages elicited by thioglycolate broth.

Acyltransferases↗

Enzyme-linked immunosorbent assay for detection of antibody to varicella-zoster virus.

Primary varicella-zoster virus (VZV) infection is a serious illness in immunocompromised individuals, and a rapid, sensitive, and reliable assay to identify high-risk VZV-susceptible patients would be clinically useful. An enzyme-linked immunosorbent assay (ELISA) for antibody to VZV was compared with the fluorescent antibody-to-membrane antigen (FAMA) assay and found to be similar in both sensitivity and specificity. The antibody titers determined by both assays were also similar. The absence of antibody detected by ELISA correlated with susceptibility to VZV infection. Because it is simple to perform and has equivalent sensitivity to FAMA, ELISA should be useful for VZV antibody testing in diagnostic and research laboratories.

Antibodies, Viral↗

Radioimmunoassay for terfenadine in human plasma.

A radioimmunoassay procedure was developed for the antihistamine terfenadine (alpha[4-(1,2-dimethylethyl)phenyl]-4-(hydroxydiphenylmethyl)-1-piperidinebutanol). The keto analog of terfenadine was converted to its O-carboxymethyloxime derivative, which was conjugated to bovine thyroglobulin by a mixed anhydride technique. Rabbits were immunized with the resulting conjugate, and antiserums capable of binding radiolabeled terfenadine were obtained. Tritium-labeled terfenadine was prepared by a combination of exchange and reduction with platinum oxide in the presence of tritium gas, and the procedure yielded a specific activity of 48 Ci/mmole. Plasma containing terfenadine was diluted with sodium carbonate solution and extracted with hexane, and the hexane extracts were evaporated and analyzed. The between-assay coefficient of variation on control samples ranged from 8% at 10 ng/ml to 14% at 1 ng/ml. The lower practical sensitivity limit was at least as low as 0.25 ng/ml (25 pg measured). Two metabolites of terfenadine cross-reacted 16-30% with the antiserum used. However, extraction eliminated essentially all of these compounds. Analysis of plasma samples from human subjects given terfenadine showed marked intersubject variability and low plasma levels.

Benzhydryl Compounds↗

Relation of Gothic arch apex to dentist-assisted centric relation.

These data suggest that the widely held belief that thumb pressure can position the mandible consistently more posterior than the position indicated by the Gothic arch apex is unfounded. Furthermore, this study provides no evidence to support the contention that the dentist-assisted jaw relation is more reproducible than the relation indicated by the Gothic arch apex.

Adult↗