Hydroxyapatite deposition disease: an uncommon cause of acute odynophagia.
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Adult↗
Biomedical subjects
R V Smith
Publications and source records attributed to R V Smith.
Cosmetic control of parotid gland hypertrophy using radiation therapy.
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Adult↗
Tumor growth and angiogenesis induced by a secreted binding protein for fibroblast growth factors.
Basic fibroblast growth factor (bFGF) is a strong inducer of angiogenesis and thus may play an important role in the growth of solid tumors. However, bFGF is usually found immobilized on the extracellular matrix, and it is only partly understood how it is solubilized to reach and activate its extracellular receptors. We studied the potential contribution to this process by a secreted binding protein (BP) with high affinity for FGFs. An expression vector for BP was transfected into a human cell line (SW-13) that contains constitutively high levels of bFGF. The BP-expressing cells began to grow colonies in soft agar due to their autocrine stimulation by bFGF and released biologically active bFGF into their media. Furthermore, they grew into well vascularized tumors in athymic nude mice. In addition, we found the BP mRNA expressed at high levels in squamous cell carcinoma (SCC) tissues from patients and in SCC cell lines of different origin as well as in immortalized keratinocytes. However, we failed to detect BP mRNA in normal adult tissues or in a number of non-SCC tumor cell lines. Expression of the secreted BP appears to be a mechanism through which immobilized FGF can be activated to support tumor growth and angiogenesis.
3T3 Cells↗
Human immunodeficiency virus: transmission concerns in clinical practice.
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Acquired Immunodeficiency Syndrome↗
[3H]dexamethasone binding to plasma membrane-enriched fractions from liver of nonadrenalectomized rats.
Using liver from nonadrenalectomized adult male rats, binding sites for [3H]dexamethasone in particulate fractions are demonstrated. The binding is thermolabile, saturable, and specific for glucocorticoid. The apparent dissociation constant (Kdapp) for [3H]dexamethasone (0.48 +/- 0.084 microM) is 60-fold greater than that for cytosolic receptor (7.9 +/- 1.5 nM). The Kdapp for [3H]cortisol in particulate fractions is 2.5-fold lower than for [3H]dexamethasone (Kdapp = 0.18 microM). The binding capacities for particulate and cytosolic glucocorticoid-binding sites also differ significantly, with particulate sites at least 9.1-fold more concentrated than cytosolic sites in liver tissue. Particulate sites are determined in Percoll density gradients to have a density of 1.039 g/cc. Saturable [3H]dexamethasone radioactivity coelutes from these gradients with the plasma membrane marker enzyme 5'-nucleotidase. Adrenalectomy causes the complete loss of particulate binding sites by 6 days postadrenalectomy; however, these sites can be regenerated to two thirds of the nonadrenalectomy level by 20-30 days postadrenalectomy.
Adrenal Glands↗
Innervation of the lung of the Australian snake-necked tortoise, Chelodina longicollis.
1. The innervation of the smooth muscle of the lung of the Australian snake-necked tortoise. Chelodina longicollis, was investigated using in vitro pharmacological techniques. 2. The smooth muscle bands of the lung were innervated by cholinergic excitatory fibres and non-cholinergic, non-adrenergic, excitatory fibres. 3. Inhibitory responses of the smooth muscle bands to transmural stimulation occurred infrequently following excitatory responses and the neurotransmitter(s) involved were not determined. Noradrenaline caused a beta-adrenoceptor mediated relaxation of the smooth muscle bands. 4. The excitatory response caused by cholinergic and non-cholinergic, non-adrenergic fibres was tetrodotoxin resistant.
Acetylcholine↗
Evidence that tracheal smooth muscle tone in guinea-pig is unaffected by overflow of noradrenaline released by perivascular nerve fibres.
1. Fluorescence histochemical techniques demonstrated that in the guinea-pig the cervical common carotid, cranial thyroid and caudal thyroid arteries were surrounded by a rich plexus of adrenergic nerve fibres. 2. The superior cervical ganglia were the source of the perivascular adrenergic fibres of the cranial thyroid arteries and the anterior half of the cervical common carotid arteries. These ganglia may also provide some of the perivascular adrenergic fibres of the caudal thyroid arteries. 3. Perivascular stimulation of the cranial thyroid and caudal thyroid arteries failed to elicit a response from isolated extrathoracic tracheal tube preparations. This suggests that it is unlikely that the guinea-pig extrathoracic trachealis muscle is innervated by adrenergic fibres arising from these perivascular plexuses or that overflow of noradrenaline from perivascular nerves causes dilatation of the trachealis muscle.
Animals↗
Development of clinical scientists.
The education and training of clinical scientists has served society in several ways. For academic pharmacy, the emergence of clinical science has provided research and scholarship opportunities for clinical faculty development. Clinical scientists have also begun to play important roles in industrial drug research and development. For all faculty and students, clinical science research reinforces a "research mindset" that will become increasingly important as our society moves from a production/extraction to an information-based economy. Pharmacy will best evolve by increasing its commitment to clinical science research. In the process, academic pharmacy must continue to improve and support excellent education and training programs for clinical scientists.
Education, Pharmacy, Graduate↗
Pharmacokinetics of orally administered pentoxifylline in humans.
The pharmacokinetics of pentoxifylline was studied in healthy male volunteers following single oral doses of 100, 200 and 400 mg of the drug in solution. Concentrations of the drug and three of its metabolites were determined in plasma. The major urinary metabolite was also determined for 24 hours after dosing. Pentoxifylline was rapidly and extensively absorbed at all doses. Peak plasma concentrations of pentoxifylline occurred between 0.29 and 0.41 hours after dosing. Its metabolites, a secondary alcohol and two homologous carboxylic acids showed tmax values from 0.72 to 1.15 hours. Cmax and AUC values increased in a dose-dependent manner for pentoxifylline and its metabolites over the three dose levels though strict dose proportionality could only be demonstrated for the principal carboxylic acid metabolite. The apparent plasma half-life of pentoxifylline varied between 0.39 and 0.84 hours for the various doses while the apparent half-lives of the metabolites were in the range of 0.96 to 1.61 hours. The major circulating metabolites, the secondary alcohol and carboxypropyl derivative, were at consistently higher plasma concentrations than the parent drug. Two major pathways account for the circulating metabolites of pentoxifylline though oxidation of the parent drug to a carboxylic acid accounts for the formation of the principal urinary elimination product. Because of the pharmacological activities of pentoxifylline, studies are proposed of the pharmacokinetic-pharmacodynamic correlations of pentoxifylline and its metabolites. The present pharmacokinetic results further support the use of a controlled-release dosage form of pentoxifylline for therapy.
Administration, Oral↗
Mechanism studies of coomassie blue and silver staining of proteins.
A relatively high complexation affinity has been found for coomassie blue G-250 and the following amino acids: arginine; tyrosine; lysine; and histidine. A linear relationship was observed between log molar absorptivity and log molecular weight of 52 of 69 proteins, polypeptides, and di- and tripeptides that were allowed to react with coomassie blue G-250 in solution. The solution complexation results were used in a study of the detection of the following model proteins: bovine serum albumin, lysozyme, recombinant DNA derived human insulin, and calmodulin. Interactions between coomassie blue stained gels and silver detection reagents were determined and used as the basis for studies of enhanced sensitivity of detection of electrophoretically developed proteins. Sensitivity enhancements of up to eight-fold were observed when various sulfonic acid dye complexed proteins were detected with silver reagents versus the use of silver reagents alone. A site-directed nucleation of silver caused by the protein complexed sulfonic acid dyes is proposed as a mechanism for the observed enhancements.
Animals↗
Determination of extrinsic pathways of adrenergic nerves to the guinea-pig trachealis muscle using surgical denervation and organ-bath pharmacology.
Intraluminal pressure changes were recorded in an isolated tracheal tube during electrical stimulation of the recurrent laryngeal nerve or transmural stimulation of the extra-thoracic trachealis muscle. The recurrent laryngeal nerve contained adrenergic nerve fibres running both anteriorly and posteriorly along this nerve and they caused an adrenergic inhibitory response of the trachealis muscle. The superior cervical ganglion was the source of the majority of the adrenergic fibres running both anteriorly and posteriorly within the recurrent laryngeal nerve. The antero-posterior adrenergic fibres reached the recurrent laryngeal nerve via an anastomosis with the superior cervical ganglion. The postero-anterior adrenergic fibres reached the recurrent laryngeal nerve via the vagus nerve, as ipsilateral vagotomy markedly reduced the inhibitory response of the trachealis muscle which had been due to the postero-anterior adrenergic fibres. Superior cervical ganglionectomy caused a significant reduction in the adrenergic response as a percentage of the total inhibitory response of the extra-thoracic trachealis muscle following transmural stimulation. The remaining response was due to stimulation of non-adrenergic non-cholinergic fibres and adrenergic fibres from another source.
Animals↗
Analysis of solvent-mediated conformational changes of insulin by radioimmunoassay (RIA) techniques.
Stationary phase radioimmunoassay (RIA) (i.e. antibodies bound to polystyrene test tubes) techniques are used as an analytical probe of secondary and tertiary structural changes of radiolabelled (125)I porcine insulin. The effects of temperature, buffer composition, pH and ionic strength and solvents on insulin binding are studied. Optimum insulin-antibody binding occurred at 22 degrees C, pH 6 and a buffer strength of 0.1 M or less. Results of experiments with three pH 6 buffers (0.005 M phosphate, 0.1 M acetate and 0.1 M Tris) showed no statistical difference in binding properties. For all solvents tested, increasing the solvent concentration decreased the amount of insulin binding. Comparison of the various solvents tested indicated that ethylene glycol and methanol are the least denaturant whilst 1-propanol and acetonitrile are among the most denaturant.
Journal Article↗
The excretion of pentoxifylline and its metabolites into human breast milk.
The methylxanthine pentoxifylline enters human breast milk after a single oral dose, with a milk-plasma ratio of 0.87 +/- 0.62 at 4 hours.
Adult↗
Ocular motility, visual acuity and dysfunction of neuropsychological impairment in children with shunted uncomplicated hydrocephalus.
Children with shunted, uncomplicated, communicating hydrocephalus were tested to determine (1) the persistence of neuropsychological impairment and (2) the relationship between neuropsychological functioning, ocular motility, and acuity abnormalities. Eighteen hydrocephalic and 18 individually age- and sex-matched controls were given a neuropsychological battery, repeated after an interval of 1 year. Hydrocephalic children were also tested at the beginning of the second year for strabismus, amblyopia and visual acuity. Their medical records were reviewed for history of ocular motility and/or acuity abnormalities. Hydrocephalic children with normal range IQ were found to have lower verbal IQ, memory, and fine motor skills compared to controls. A history of ocular motility and acuity abnormalities was associated with impaired visuospatial and verbal problem-solving skills.
Achievement↗
Silver staining of proteins in polyacrylamide gels: increased sensitivity through a combined Coomassie blue-silver stain procedure.
A combined Coomassie blue-silver stain method has been developed in sodium dodecyl sulfate-polyacrylamide gels for the detection of proteins using the model compounds bovine serum albumin, lysozyme, and recombinant DNA-derived human insulin. Sensitivity was enhanced 2.2 to 8.6 times by the new method relative to that of silver staining alone. The new method may also be useful in enhancing detection sensitivities of other proteins.
Electrophoresis, Polyacrylamide Gel↗
Extrinsic pathways of the adrenergic innervation of the guinea-pig trachealis muscle.
Origins and extrinsic pathways of the adrenergic innervation of the guinea-pig trachealis muscle were studied using fluorescence histochemical techniques. Bilateral superior cervical ganglionectomy caused a marked reduction in the adrenergic innervation of the extra-thoracic region, which suggests that these ganglia are a major source of adrenergic innervation to this muscle. Combined anterior and posterior transection of the recurrent laryngeal nerves also caused a marked reduction in the density of adrenergic fibres in the extra-thoracic trachealis muscle. Crushing of these nerves revealed adrenergic fibres running both anteriorly and posteriorly. The majority of these adrenergic nerves were lost after superior cervical ganglionectomy and thus the fibres running in both directions originate in the superior cervical ganglion. Antero-posteriorly directed fibres entered the recurrent laryngeal nerve from the superior cervical ganglion via an anastomosis at the level of the cricoid cartilage, while those running postero-anteriorly entered the recurrent laryngeal nerve posteriorly from the vagus nerve and these adrenergic fibres were lost after cervical vagotomy.
Adrenergic Fibers↗
Comparison of extraction and precipitation methods for the HPLC determination of furosemide in plasma and urine.
Comparisons have been made between an ether extraction method and an acetonitrile precipitation method for the HPLC determination of furosemide (frusemide) in human plasma and urine. Recoveries of furosemide were 81-89% (ether extraction method for plasma), 73-103% (acetonitrile precipitation method for plasma) and 62-89% (ether extraction method for urine) for the concentration ranges studied. Values of correlation coefficients were 0.9998, 0.9991 and 0.9997 for standard curves for the three methods, respectively. Accuracy and precision (RSD) were: 92.4-114% +/- 3.57-20% for ether-extracted plasma; 98.1-103% +/- 3.47-19.9% for acetonitrile-precipitated plasma; and 103-107% +/- 4.03-13.2% for ether-extracted urine. Because of carryover of endogenous urine components, the acetonitrile-precipitation assay was unacceptable for urine. Furosemide was stable in frozen plasma for at least 113 days and in frozen urine for at least 204 days. No artifactual appearance of the hydrolysis product of furosemide, 4-chloro-5-sulfamoylanthranilic acid (CSA), was detected by the ether-extraction method under normal assay conditions.
Journal Article↗
Interactions of apomorphine with serum and tissue proteins.
Physical and covalent interactions of apomorphine with serum and tissue proteins could influence the drug's disposition and pharmacological activities in mammals. Ultrafiltration, equilibrium dialysis, and ultraviolet spectrophotometric methods have been used to study the reversible binding of apomorphine to bovine, human, rat, and swine plasma proteins. The degree of binding was generally greater than 90%, but variations were noted in some instances on the basis of drug concentrations and pH over the range of 6.8-7.8. Incubation of [8,9-3H2]apomorphine with bovine serum albumin led to retention of radioactivity and a stoichiometrically controlled released of tritium which arose from the reaction of an electrophilic drug oxidation product and protein, producing drug-protein conjugates. In vitro experiments with mouse striatal brain preparations indicated parallel covalent binding reactions. In vivo experiments in mice indicated accumulation of radioactivity in brain regions and other tissues following daily injections of [8,9-3H2]apomorphine for 14 days. The physical and covalent interactions of apomorphine with mammalian tissue proteins could be the cause of longer disposition half-lives in mammals than those previously reported. The covalent interactions, in particular, may be important in elucidating the mechanism of apomorphine-induced behavioral effects in mice.
Animals↗