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Biomedical subjects

R M Lee

Publications and source records attributed to R M Lee.

At least 127 records · Page 7Linked to original sources
PubMed1984

The pharmacokinetics in man of SK&F 93319--a new antagonist of histamine H1 and H2 receptors.

SK&F 93319, a potent histamine H1- and H2-receptor antagonist, is rapidly absorbed with a low rate of plasma clearance primarily by metabolism. Excretion is divided evenly between urine and faeces (probable biliary elimination) with little unchanged drug in the urine. Serum protein binding at low concentrations is very extensive and appears to restrict distribution of SK&F 93319. At higher concentrations (higher dose levels) reduced protein binding results in a marked proportional increase in available free drug with a consequent increase in distribution and clearance. Bioavailability is reduced at higher dose levels. The importance of factors contributing to non-linear pharmacokinetics and the potential clinical consequences are demonstrated.

Adult↗
PubMed1984

Trypan blue method for the identification of areas of damage to airway epithelium due to mechanical trauma.

A method has been developed for locating the regions of pulmonary epithelial damage due to mechanical trauma, based on the inability of the injured cells to exclude vital stains such as trypan blue. Scanning electron microscopy was used to confirm the sites, as well as the specific type of mechanical damage. The damaged area on rabbit tracheal epithelium due to gentle stroking was characterized by denudation of the ciliated epithelial cells, leaving only a layer of flat, non-ciliated cells. Repeated gentle stroking of the epithelial surface removed all the epithelial cells, exposing the underlying connective tissue layer. The trypan blue method provides a fast and sensitive means of locating damaged airway epithelium due to mechanical trauma. Because the dye is non-toxic, the repair process of the epithelium can also be studied, following the initial assessment of the extent of epithelial damage.

Animals↗
PubMed1983

The assay of a novel histamine H2-receptor antagonist, SK&F 93479, in human plasma by normal-phase high-performance liquid chromatography.

A selective assay of a new histamine H2-receptor antagonist, SK&F 93479, in human plasma has been developed. The method uses liquid-liquid extraction from the biological sample and analysis of the resulting extract by normal-phase high-performance liquid chromatography with UV detection for quantitation of the drug and an added standard. The assay is sufficiently accurate and precise to determine the compound at concentrations as low as 0.025 mg 1(-1). The coefficient of variation of the assay averages 5.7% at concentrations between 0.1 and 2.0 mg 1(-1), but increases to 21.8% at 0.02 mg 1(-1). SK&F 93479 can be determined in spiked plasma samples, at concentrations between 0.05 and 0.80 mg 1(-1) with a bias of between -7.5 and +3.6%, but at 0.02 mg 1(-1) concentrations were underestimated by 15% on average. The assay has been used for pharmacokinetic and bioavailability studies: after a single 0.5 mg kg-1 oral dose in man, plasma concentrations can be monitored for up to 70 h after dosing.

Chromatography, High Pressure Liquid↗
PubMed1983

Comparison of two high-performance liquid chromatographic methods for the determination of oxmetidine and its metabolites in plasma, bile and urine samples.

Two high-performance liquid chromatographic methods for the assay of oxmetidine are described: both utilize the same liquid extraction from plasma, urine and bile samples. A normal-phase technique is considered most suitable for the analysis of plasma extracts and a reversed-phase method is preferred for the assay of excretory fluids such as urine and bile which will contain polar metabolites in detectable quantity as well as unchanged oxmetidine The methods are sensitive enough to follow the kinetic changes in concentration for up to 8 h after the administration of recommended therapeutic doses. Both methods can be automated in respect of the high-performance liquid chromatograph and the samples can be stored for several weeks at -20 degrees C without prejudicing the accuracy of the analysis.

Bile↗
PubMed1983

Discrimination of systolic blood pressure.

The ability of humans to discriminate systolic blood pressure (BP) was investigated in two experiments. In Experiment 1, 14 normal subjects were asked to make estimates of their systolic BP while performing both BP-elevating and BP-lowering tasks. They were given intermittent feedback throughout all 10 45-min sessions. Results indicated significant correlations and small absolute differences between estimated and measured BP for all subjects in almost all sessions. Experiment 2, undertaken 6 months after Experiment 1, assessed whether estimation accuracy by subjects who had available both external and interoceptive cues surpassed that of subjects which access to external cues only. Three subjects from the original group who showed consistently high motivation, and who improved in accuracy across the 10 sessions in the previous experiment, made estimates of BP while performing novel tasks with no feedback. Correlations between estimated and measured BP remained high for 2 of the 3. These results were compared with the accuracy of control subjects (3 for each experimental subject) who were asked to estimate experimental subjects' BP using only the cognitive information available to the experimental subjects. Control subjects also had high correlations between their estimates and the experimental subjects' measured BP but at lower levels than two experimental subjects. These findings are discussed in relation to subjects' possible use of interoceptive information.

Adolescent↗
PubMed1983

An analytical approach to the preparation and characterization of subcellular membranes from canine mesenteric arteries.

Subcellular membrane fractions were isolated from dog mesenteric arteries by differential and isopynic sucrose density gradient centrifugations. Isolated membrane fractions were characterized by marker enzyme activities, morphological features and sodium dodecyl sulfate-polyacrylamide gel electrophoretic patterns. Our results show that the microsomal fraction isolated by conventional differential centrifugation was highly heterogenous and contained substantial amount of plasma membranes which could be further enriched as a light density membrane fraction on a discontinuous sucrose density gradient. The microsomal fraction and its subfractions were vesicular in appearance under electron microscope and were capable of binding and actively transporting Ca2+. The binding of Ca2+ and ATP-supported Ca2+-transport in the presence or absence of oxalate paralleled the distribution of plasma membrane marker enzyme activities suggesting that plasma membranes in vascular smooth muscle may play a major role in handling Ca2+ and thus the control of contractile function.

Adenosine Triphosphate↗
PubMed1983

Morphometric study of structural changes in the mesenteric blood vessels of spontaneously hypertensive rats.

Structural changes of three categories of mesenteric arteries (representing elastic, muscular and arteriolar vessels) from 10- to 12-week-old and 28-week-old spontaneously hypertensive rats (SHR) were studied morphometrically at the light microscope level, and the results compared with age-matched Wistar-Kyoto normotensive rats. In 10- to 12-week-old SHR, hypertrophy of the vessel wall occurred only in the muscular and arteriolar vessels. At 28 weeks, further thickening of the vessel wall occurred in the muscular and arteriolar vessels, and the superior mesenteric artery (elastic vessel) was also thickened in the SHR. There was no evidence that the wall of the relaxed hypertrophied vessels encroached upon the lumen of the vessel. The structural basis for the increase in the vessel wall thickness varied with vessel type. In the superior mesenteric artery, increase in the media at 28 weeks of age would be consistent with hypertrophy of the smooth muscle cells. In the large muscular arteries, at 10-12 weeks of age, increase in medial mass occurred with increase in the number of the smooth muscle cell layers whereas at 28 weeks further increase in media could be due to hypertrophy of the smooth muscle cells. In the small arteriolar vessels, medial enlargement was due at all ages to an increase in the number of smooth muscle layers. Our results show that in the SHR hypertrophy of the media occurs not only in the small arteriolar vessels, but also in large elastic and muscular arteries.

Animals↗
PubMed1983

Ultrastructural changes in mesenteric arteries from spontaneously hypertensive rats. A morphometric study.

Morphometric measurements at the electron microscope level were carried out on three categories of mesenteric arteries representing elastic (superior mesenteric), muscular and arteriolar vessels, from 10- to 12-week-old spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto normotensive rats (WKY). Changes were observed only in muscular and arteriolar vessels of SHR, mainly as thickening of the vessel wall due to hypertrophy of the media. In muscular arteries, hypertrophy of the endothelial cells, widening of the subendothelial space, increased volume of the internal elastic lamina (IEL), and both hyperplasia and hypertrophy of the smooth muscle cells (SMC) in the media contributed to the wall thickening. In arteriolar vessels, increase in the subendothelial space and IEL, and hyperplasia of the SMC in the media were involved in the increased thickness of the vessel wall. There was no difference in the collagen content in all vessels, but elastin was increased in the muscular and arteriolar vessels of SHR. Nerve density was also increased in arteriolar vessels of SHR. These changes, especially the increase of SMC in muscular and arteriolar vessels, may be related to the elevated blood pressure in SHR.

Animals↗
PubMed1983

Comparison of blood vessel wall dimensions in normotensive hypertensive rats by histometric and morphometric methods.

The histometric method is often used in hypertension studies in order to reconstruct, from cross-sectional profiles of vessels in the contracted state, a hypothetical relaxed state of the vessels based on the measured length of the internal elastic lamina (IEL). In this study, the accuracy of the histometric method was tested by comparing values obtained with the histometric method from contracted vessels versus values from morphometric measurements of vessels of the same calibre but maximally relaxed. Mesenteric arteries from spontaneously hypertensive and normotensive Wistar-Kyoto rats were used. We found that the lumen size of the vessels was dependent on the methods of measurement and preparation. Lumen size, determined with the histometric method from contracted vessels, tended to be underestimated mainly because the IEL became shortened during contraction of the vessels. When vessels were prepared by perfusion fixation, a high perfusion flow rate (7.6 ml/min) caused expansion of the lumen in muscular (lumen diameter 120--250 microns) and arteriolar vessels (40--100 microns), but not in the elastic arteries (400--700 microns). The cross-sectional area of the vessel wall, however, remained unchanged when the vessels were either contracted with norepinephrine or expanded with high transmural pressure, so morphometric measurements of the vessel wall and its components can be done on both contracted and relaxed vessels. Our results suggest that the use of the histometric method for the estimation of relaxed lumen size from the contracted vessels is of very limited value. We also suggest that, for an accurate comparison of vessel wall dimensions between hypertensive and normotensive animals, cross-sectional area should be used instead of wall thickness alone.

Animals↗
PubMed1983

Nasal cilia in normal man, primary ciliary dyskinesia and other respiratory diseases: analysis of motility and ultrastructure.

We studied the ultrastructure and function of nasal cilia from non-atopic and atopic non-smokers, smokers, patients with chronic rhinitis and cystic fibrosis, and compared these to cilia from patients with primary ciliary dyskinesia (PCD). Atypical cilia were found in normal subjects and patients with a variety of chronic respiratory tract diseases, but the proportion was small (less than 5%). Ciliary wave form, beat frequency, and mucociliary transport were normal. In patients with PCD, the proportion of atypical cilia and ultrastructural abnormalities was significantly greater than normal subjects and patients without PCD p less than 0.0001. Beat frequency was reduced, ciliary wave form was grossly abnormal, and mucociliary transport was virtually absent. These findings suggest that ciliary ultrastructural abnormalities are related to altered ciliary function and have aetiological relevance in the generalized chronic respiratory tract disease of PCD.

Cilia↗
PubMed1982

Effects of glutaraldehyde fixative osmolarities on smooth muscle cell volume, and osmotic reactivity of the cells after fixation.

The contribution of glutaraldehyde (GA) to the effective osmolarity of GA fixatives, the osmotic reactivity of the cells after fixation in GA, and also the duration of fixation in GA on cell volume, were investigated using cultured smooth muscle cells (SMC) and spiral aortic strips. Four fixation procedures were studied. We found that GA contributes to the total effective osmolarity of the fixatives, and that the type of buffers used for the fixatives can also affect the cell volume differently during GA fixation. After GA fixation, the cells were still osmotically reactive, regardless of the buffer types for making up the GA fixatives, so that the osmolarity of the wash buffer after GA fixation is important. However, OsO4 eliminates osmotic responses, thus the osmolarity of OsO4 fixative and wash buffer have negligible influence on the cell volume. Longer fixation time up to 4 h had no effect of the cell volume.

Aldehydes↗
PubMed1982

A simple method for the handling and orientation of small specimens for electron microscopy.

Cyanoacrylic glue (Eastman 910) was used to affix small pieces of nasal scrapings to lens paper immediately before fixation in the glutaraldehyde. The lens paper not only served to hold specimens together so that they were not lost during tissue processing, but also functioned as a 'landmark' for the specimens, so that specimens could be oriented in a specific manner during embedding and subsequent sectioning.

Adhesives↗
PubMed1981

Isolation of plasma membranes from rat mesenteric veins: a comparison of their physical and biochemical properties with arterial membranes.

Plasma membranes were isolated from smooth muscles of rat mesenteric veins. The plasma membrane fraction is relatively pure according to its morphological and enzymatic characteristics. The membrane distribution, enzymatic activities, as well as calcium accumulation by the plasma membrane fraction from venous smooth muscle were compared to those from arterial smooth muscle. The isolated venous smooth muscle plasma membranes formed primarily closed vesicles which were capable of accumulating Ca2+ in the presence of ATP suggesting active transport of Ca2+ across the membrane vesicles. Evidence obtained from several approaches by studying the effect of A23187, phosphate ions and hypotonic shock on the Ca2+ accumulation in the presence of ATP revealed that there is an active transport of Ca2+ across isolated vascular smooth muscle membrane vesicles in addition to binding of Ca2+. However, venous smooth muscle plasma membrane fraction appears to be different from arterial smooth muscle plasma membrane fraction in its low activity of alkaline phosphatase, greater Ca2+ binding and lower Ca2+ transport. These and previous studies show that the plasma membrane of vascular muscles may play an important role in the steady state regulation of cellular calcium concentration during excitation-contraction coupling, especially in small arteries and veins.

Adenosine Triphosphate↗
PubMed1980

Dimensional changes of cultured smooth muscle cells due to preparatory processes for transmission electron microscopy.

The change in volume of cultured smooth muscle cells prepared with four different fixation procedures for transmission electron microscopy was studied. Although the cells showed swelling after being embedded in Spurr's embedding medium, the degree of swelling depended on the particular method of fixation procedure used. When the volume of the cells measured using transmission electron microscopy was compared with that of the fresh cell volume, cells prepared by two of the methods showed swelling, and cellular shrinkage was noted in the other two methods. One method which caused the least amount of volume change is recommended for quantitative electron microscopic study of vertebrate smooth muscle cell systems.

Animals↗
PubMed1980

The dyskinetic cilia syndrome. Ciliary motility in immotile cilia syndrome.

Ciliary motility was studied in three patients with Kartagener syndrome who had previously been found to have absent nasal and pulmonary mucociliary transport and missing dynein arms in nasal cilia. A video system was used to record movement of cilia obtained by nasal brushings for analysis of wave form and beat frequency. Two patterns of abnormal ciliary beat were observed; an oscillating and a rotating type of motion. There was no evidence of planar coordination of metachronicity. This abnormal motion was present in up to 40 percent of cells and the remainder were totally immotile. Thus, in Kartagener syndrome many ciliated cells are motile, but the motion is abnormal. We suggest that "immotile cilia syndrome" is a misnomer, and recommended it be renamed "dyskinetic cilia syndrome."

Adenosine Triphosphatases↗