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Biomedical subjects

R L Jones

Publications and source records attributed to R L Jones.

At least 289 records · Page 16Linked to original sources

Time course of reversibility of accelerated fibrinogen disappearance in diabetes mellitus: association with intravascular volume shifts.

Accelerated fibrinogen disappearance in diabetic patients is reversible with normalization of blood glucose. To define the time course of this reversal, we measured 125I-fibrinogen disappearance in 19 diabetic patients experiencing acute changes in blood glucose, as monitored and controlled by a microprocessor-controlled closed loop insulin infusion system (artificial beta cell). The data were corrected for blood volume dilutional changes and fit to a model describing two sequential exponential functions and a single exponential function. The sequential model provided the best fit for all but one patient. This indicates that there were two distinct rates of fibrinogen disappearance and suggests that the time course of reversal of accelerated fibrinogen disappearance in diabetic patients is very rapid, if not immediate. Rapid fibrinogen turnover during hyperglycemia was temporally associated with vascular volume changes, reflected as dilutional changes of 51Cr-RBC concentrations. These findings were also associated with an increase in pulse pressure during hyperglycemia, suggesting blood volume expansion due to an osmotic mechanism. The results of this study suggest a picture of vascular volume expansion and contraction, perhaps secondary to the osmotic effects of hyperglycemia. Accelerated fibrinogen turnover associated with these events may be related to increased vascular permeability and/or increased fibrin formation. These events, in concert, may contribute to the initiation and/or propagation of diabetic vascular sequelae.

Adolescent↗

Brucella abortus antigen-induced lymphocyte reactivity in guinea pigs.

A whole blood lymphocyte transformation (WBLT) assay was used to detect anti-brucella lymphocyte reactivity in guinea pigs. Brucella antigens stimulated an antigen-specific lymphoproliferative response in WBLT assays from Brucella abortus infected guinea pigs. The response was best detected from 6 to 16 weeks after challenge inoculation with viable B. abortus 2308. Lymphocytes were not stimulated by unrelated bacterial antigens and control animals did not respond to the Brucella antigens. The responding cell population was characterized as mostly T lymphocytes. The WBLT assay was found to be specific for the detection of anti-brucella lymphocyte reactivity. However, a negative response was not definitive, which indicated a need for repeated testing to establish that a guinea pig did not have anti-brucella lymphocyte sensitization.

Animals↗

Breath ethyl alcohol concentration and analysis in the presence of chronic obstructive pulmonary disease.

We have made continuous measurements of exhaled ethanol concentration vs volume during slow expiration in subjects with plasma ethanol concentrations up to 700 mg/L. Subjects included individuals with normal pulmonary function and those with severe chronic obstructive pulmonary disease (COPD). In addition to the measurements of breath ethanol made using a flame ionization detector, paired measurements were also made of plasma ethanol and breath ethanol using a Model 900A Breathalyser. In normal subjects, the breath ethanol concentration was found to increase continuously during expiration until the very end of the expiration when a decline in concentration was noted. In the presence of COPD the ethanol concentration/volume tracing was essentially flat during the middle portion of expiration, but many subjects showed a decrease in concentration at the end of the expiration. One subject showed a sharp rise in breath concentration at the end of expiration. The results suggest that fluctuations in the ethanol concentration are caused by variation in the ventilation/perfusion ratio of regions of the lung supplying the expirate, and that breath with ethanol in equilibrium with the plasma is not routinely obtained, especially at the end of a maximal expiration. Thus, exhaled air at the end of maximal expiration does not always provide the best, or a close, indication of the plasma (or blood) ethanol concentration. The peak breath ethanol concentrations found were, as an equivalent plasma concentration, = -25 + 0.924 X plasma ethanol, mg/L. The Breathalyser readings = -45 + 0.898 X plasma ethanol, mg/L, with a mean difference of -81 mg/L.

Adult↗

Infiltration of the supraorbital nerve by basal cell carcinoma.

A case report is presented of a man with a recurrence of a basal cell carcinoma on the forehead that upon histologic examination of the specimen of surgical excision revealed both perineurial and endoneurial invasion of several fascicles of the supraorbital nerve by neoplastic cells.

Basal Cell Carcinoma↗

The importance of elastic fibres in skin lymphatics.

Elastic fibres lie in intimate contact with dermal lymphatics. Demonstration of elastic by an orcein stain enables lymphatics to be identified and differentiated from blood capillaries. The finding of elastic suggests it plays an important role in the normal functioning of lymphatics.

Animals↗

Ligand binding to thromboxane receptors on human platelets: correlation with biological activity.

The preparation of enantiomerically pure [3H]-15 (S) 9, 11-epoxymethano PGH2 (a thromboxane A2-like agonist) has enabled the binding of ligands to the thromboxane receptor of the human platelet to be studied. The binding of the radio-ligand to washed human platelets has 3 components. One component is not displaceable by 'cold' 9, 11-epoxymethano PGH2 and its concentration-binding plot is roughly linear. The other 2 components are displaceable and saturable, and the larger of the two, which is sensitive to the stereochemistry of the C15 secondary alcohol, appears to represent the thromboxane receptor. About 1700 15(S)9, 11-epoxymethano PGH2 molecules are specifically bound to a single platelet and 50% of this binding is achieved with a concentration of 75 nM. Displacement of [3H]-15(S)9, 11-epoxymethano PGH2 is effected by (a) TXA2 and PGH2 and a number of bicyclic stable analogues (e.g. 9,11-azo PGH2), all of which produce irreversible aggregation of human platelets; (b) analogues of PGF2 alpha with potent thromboxane-like activity (e.g. ICI 79939); (c) compounds with partial agonist activity on the platelet thromboxane system (e.g. CTA2); (d) Thromboxane/endoperoxide analogues which specifically antagonize thromboxane-like actions on the human platelet (e.g. PTA2 and EP 045). Displacement is not achieved with the natural prostaglandins PGE2, PGD2 and PGF2 alpha. Neither the thromboxane-synthetase inhibitor dazoxiben nor R(+)-trimethoquinol have high displacing activity. The correlation of radio-ligand displacement with the biological activity of the competing ligands is discussed in relation to the nature of the thromboxane receptor on the human platelet.

Binding, Competitive↗

A serologic survey of brucellosis in white-tailed deer (Odocoileus virginianus) in Missouri.

During the hunting seasons of 1979 and 1980, sera were collected from 713 white-tailed deer in Missouri and tested for antibodies to Brucella abortus using the standard tube agglutination, standard plate agglutination, Brucella buffered antigen card agglutination and rivanol agglutination tests. Only one sample was considered to be positive for Brucella antibodies. This study demonstrated that white-tailed deer in Missouri were not an important reservoir host of brucellosis.

Agglutination Tests↗

Erythrocyte membrane 2', 3'-cyclic nucleotide 3'-phosphodiesterase activity in multiple sclerosis.

The specific activities of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase, EC3.1.4.37) in erythrocyte membranes from five patients with active multiple sclerosis (MS) and five normals were compared. The CNPase assay used 2',3'-cyclic NADP as the substrate in an enzyme coupled reaction to produce fluorometrically detectable NADPH. The specific activity of CNPase in the MS and normal groups were 19.2 +/- 2.3 and 28.7 +/- 1.8 mumol/h/mg protein, respectively. The difference was significant with p less than 0.006, based on a one-tailed t-test.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

Viscometric analysis of the interaction of bisphenanthridinium compounds with closed circular supercoiled and linear DNA.

The interaction with closed circular supercoiled and linear DNA of bisphenanthridinium compounds substituted through both the meta and para positions of the 6-phenyl group, along with appropriate monomer intercalators as controls, has been investigated by viscometric titration. When CPK models for the phenanthridinium rings of the three bis-compounds are oriented in a parallel manner as a model for intercalation, their ring plane to ring plane distances are approximately 7 to 8 A (SR 2430), 11 A (SR 2193), and 15 A (SR 2166). In SR 2430 the two phenanthridines are linked through the para positions of the 6-phenyl group; this chain allows intercalation of the two rings at adjacent binding sites in DNA, but is not long enough to accommodate an excluded site. The viscometric titrations with both superhelical and linear DNA clearly indicate that SR 2430 gives results close to those of the monomer control compounds while SR 2193 and SR 2166 have approximately twice the unwinding angle and DNA length increase on binding to DNA as the monomer compounds. These phenanthridinium compounds, therefore, are capable of bisintercalation only if their linking groups are of sufficient length to allow an excluded binding site between base pairs. This conclusion is supported by DNA thermal denaturation experiments in the presence of these compounds.

Chemical Phenomena↗

Interaction of actinomycin D, ethidium, quinacrine, daunorubicin, and tetralysine with DNA: 31P NMR chemical shift and relaxation investigation.

The binding of actinomycin D, ethidium, quinacrine, daunorubicin, and tetralysine to DNA has been investigated using 31P NMR. Titration of DNA with actinomycin yields a new downfield peak or overlapping peaks as would be expected from the slow dissociation kinetics of this compound. The other intercalators shift the DNA 31P signal downfield as a single exchange averaged peak. Tetralysine causes a slight upfield shift. The chemical shift titration curves for the intercalators are sigmoid curves suggesting that cooperative processes or competing effects on the chemical shift are being observed. The magnitude of the chemical shift change at saturation of DNA with the compounds is found to vary significantly and to be linearly related to the DNA base pair unwinding angle for the compounds. Analysis of 31P spin lattice relaxation times (T1) and linewidths as a function of temperature (below Tm) and titration with the above compounds indicates that T1 does not change significantly while linewidth increases with decreasing temperature and increasing bound intercalator. One interpretation of these results is that in both cases the overall motion of DNA becomes slower while the internal motion is not greatly affected.

Animals↗

Synthesis of prostanoids with bicyclo[2.2.1]heptane, bicyclo[3.1.1]heptane, and bicyclo[2.2.2]octane ring systems. Activities of 15-hydroxy epimers on human platelets.

A number of prostanoids with bicyclo[2.2.1]heptane, bicyclo[3.1.1]heptane, and bicyclo[2.2.2]octane ring systems have been prepared by routes which allow the introduction of the omega chain after the alpha chain. The introduction of a 16-p-halophenoxy substituent confers platelet aggregation activity on both 15 alpha- and 15 beta-hydroxy epimers. In the case of the pinane thromboxane ring system, the natural omega-chain compound is an inhibitor of aggregation, whereas the 16-p-fluorophenoxy analogue is a potent aggregation agent.

Bridged Bicyclo Compounds↗

Effect of IAA on Growth and Soluble Cell Wall Polysaccharides Centrifuged from Pine Hypocotyl Sections.

Auxin-induced elongation and cell wall polysaccharide metabolism were studied in excised hypocotyl sections of ponderosa pine (Pinus ponderosa) seedlings. Sections excised from hypocotyls of ponderosa pine elongate in response to the addition of auxin. The neutral sugar composition of the extracellular solution removed from hypocotyl sections by centrifugation was examined. In cell wall solution from freshly excised sections, glucose, galactose, xylose, and arabinose make up more than 90% of the neutral sugars, while rhamnose, fucose, and mannose are relatively minor components. The neutral sugar composition of the polysaccharides of the pine cell wall solution is both qualitatively and quantitatively similar to that of pea. Following auxin treatment of pine hypocotyls, the neutral sugar composition of the cell wall changes; glucose, xylose, rhamnose, and fucose increase by nearly 2-fold relative to controls in buffer without auxin. These changes in neutral sugars in response to auxin treatment are similar to those found in pea, with the exception that in pea, rhamnose levels decline in response to auxin treatment.

Journal Article↗

Alpha-amylase secretion by single barley aleurone layers.

The secretion of alpha-amylase from single isolated (Hordeum vulgare L. cv Himalaya) aleurone layers was studied in an automated flow-through apparatus. The apparatus, consisting of a modified sample analyzer linked to a chart recorder, automatically samples the flow-through medium at 1 minute intervals and assays for the presence of alpha-amylase. The release of alpha-amylase from aleurone layers begins after 5 to 6 hours of exposure to gibberellic acid and reaches a maximum rate after 10 to 12 hours. The release of alpha-amylase shows a marked dependence on Ca(2+), and in the absence of Ca(2+) it is only 20% of that in the presence of 10 millimolar Ca(2+). Withdrawal of Ca(2+) from the flow-through medium results in the immediate cessation of enzyme release and addition of Ca(2+) causes immediate resumption of the release process. The effect of Ca(2+) is concentration-dependent, being half-maximal at 1 millimolar Ca(2+) and saturated at 10 millimolar Ca(2+). Ruthenium red, which blocks Ca(2+) but not Mg(2+) efflux from barley aleurone layers, renders alpha-amylase release insensitive to Ca(2+) withdrawal. Inhibitors of respiratory metabolism cause a burst of alpha-amylase release which lasts for 0.5 to 5 hours. Following this phase of enhanced alpha-amylase release, the rate of release declines to zero. Pretreatment of aleurone layers with HCl prior to incubation in HCN also causes a burst of alpha-amylase release, indicating that the inhibitor is affecting the secretion of alpha-amylase and not its movement through the cell wall. The rapid inhibition of alpha-amylase release upon incubation of aleurone layers at low temperature (5 degrees C) or in 0.5 molar mannitol also indicates that enzyme release is dependent on a metabolically linked process and is not diffusion-limited. This conclusion is supported by cytochemical observations which show that, although the cell wall matrix of aleurone layers undergoes extensive digestion after gibberellin treatment, the innermost part of the cell wall is not degraded and could influence enzyme release.

Journal Article↗

Effects of prostaglandins and thromboxane analogues on bullock and dog iris sphincter preparations.

1 The bullock iris sphincter was contracted by low concentrations of prostaglandin E2 (PGE2), 16, 16-dimethyl PGE2 and 17,18,19,20-tetranor-16-p-chlorophenoxy PGE2. Other compounds with thromboxane-like actions, for example 11,9-epoxymethano PGH2, were also potent spasmogens, ZK 36374, a stable carbacyclin, was a partial agonist on the PGE-sensitive system of this tissue. 2 The thromboxane antagonist, EP 045, had little effect on the action of PGE2 and 16,16-dimethyl PGE2 on the bullock iris. 3 The dog iris sphincter was sensitive to PGF2 alpha but not to PGE2 and 11,9-epoxymethano PGH2. 4 16,16-dimethyl PGE2 had very low activity on the dog iris in contrast to its high activity on the bullock iris. The reverse was found with the 17,18,19,20-tetranor-16-m-trifluoromethylphenoxy analogue of PGF2 alpha (ICI 81008). This indicates a considerable selectivity of action of the two analogues. 5 The results are discussed in relation to the existing knowledge of prostanoid receptors.

Animals↗

Antagonism of the thromboxane-sensitive contractile systems of the rabbit aorta, dog saphenous vein and guinea-pig trachea.

1 The thromboxane-sensitive contractile systems in spirally-cut preparations of the rabbit aorta, dog saphenous vein and guinea-pig trachea have been compared. The full or partial agonist activities of a range of bicyclic ring analogues were found to be remarkably similar on the three preparations. In addition, EP 045, a prostanoid with a phenylsemicarbazone omega-chain, blocked the action of both thromboxane A(2) (TXA(2)) and the bicyclic ring analogues. Using 11,9-epoxymethano prostaglandin H(2) as the agonist, linear Schild plots with slopes close to unity were obtained on each preparation; this suggests a competitive type of antagonism.2 Analogues of prostaglandin D(2) (PGD(2)), PGE(2) and PGF(2alpha) also contracted the three smooth muscle preparations; those analogues containing a 16-p-halophenoxy residue were highly active. On the rabbit aorta, EP 045 completely blocked the contractile actions of these agonists, perhaps indicating a single type of prostanoid receptor in this tissue. On the dog saphenous vein PGD(2), PGE(2) and 15-methyl PGE(2) exhibited relaxant activity when the tissue was partially contracted with either a thromboxane agonist or noradrenaline. On the guinea-pig trachea 16,16-dimethyl PGE(2) and the 16-p-chlorophenoxy analogue of PGE(2) were potent contractile agents whose action was not blocked by EP 045. PGE(2) and 15-methyl PGE(2) showed similar properties but exhibited relaxant activity with increasing concentrations in the organ bath. Our results indicate the presence of three types of prostanoid receptors in the guinea-pig trachea: thromboxane- and PGE-sensitive systems mediating contraction and a PGE-sensitive system mediating relaxation.3 The similarity of the thromboxane-sensitive systems in the three smooth muscle preparations is discussed with particular reference to the differences in the equilibrium dissociation constants for EP 045.

Animals↗