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Biomedical subjects

R L Jones

Publications and source records attributed to R L Jones.

At least 235 records · Page 13Linked to original sources
PubMed1986

Hematin-derived anticoagulant. Generation in vitro and in vivo.

Prolongation of clotting times produced by hematin was investigated both in vitro and in vivo. Hematin-derived anticoagulant (HDA) was found to be due to a degradative product or derivative of hematin, and was generated in vitro in standing (aging) aqueous solutions of the parent compound. Generation of HDA in vitro was inhibited by antioxidants. The anticoagulant effect of HDA was inhibited by freshly prepared hematin, fresh Sn-protoporphyrin, imidazole, or the iron chelator desferrioxamine. Ferrioxamine did not inhibit HDA, and inhibition by imidazole was reversed with ferric citrate, suggesting a role for iron in the mechanism of HDA activity. HDA activity was dissociated from hematin in plasma by clotting with thrombin. HDA segregated into the clot fraction, whereas hematin remained largely in the serum fraction, suggesting that HDA may preferentially bind to fibrinogen. TLC and HPLC showed a single peak of HDA activity that was not associated with the parent compound. Evidence for HDA generation in vivo was found when rats were injected with fresh (no HDA) hematin. Prolongation of clotting times appeared after hematin appeared in the plasma, and anticoagulant activity persisted after a fall in plasma hematin concentration. Thus, there was a temporal dissociation between hematin and HDA, suggesting that a modification of hematin must occur in vivo before an anticoagulant effect is produced. Generation of HDA in vitro has implications for hematin preparation and administration. Generation of HDA in vivo suggests that similar modifications of endogenous heme or other porphyrins may occur to produce HDA under physiologic or pathophysiologic conditions.

Anticoagulants↗
PubMed1986

Increased platelet thromboxane receptor sensitivity in diabetic patients with proliferative retinopathy.

Platelet aggregation to collagen in 12 Type 1 (insulin-dependent) diabetic patients with background retinopathy and 12 Type 1 diabetic patients with proliferative retinopathy was compared with an age- and sex-matched control group. An analogue of prostaglandin H2, 11,9 epoxymethano-prostaglandin H2, which directly stimulates thromboxane receptors, and EP 092, which is a competitive thromboxane A2 receptor antagonist, were used to investigate changes at platelet thromboxane receptor level in these groups. The concentration of collagen (EC50) required to give 50% of maximum aggregation did not differ between the two diabetic groups and the control group. However, platelets from the proliferative retinopathy group were significantly more sensitive to the thromboxane mimetic (11,9 epoxymethano-prostaglandin H2) (p less than 0.005) than the background retinopathy and control groups. This change may be a factor in the development of proliferative retinopathy.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1986

Vascular sensitivity to prostaglandin I2 and urinary excretion of 6-keto-prostaglandin F1 alpha in conscious dogs.

A method is described for measuring the urinary excretion of 6-keto-prostaglandin F1 alpha, the stable hydrolysis product of prostaglandin I2, by stable isotope dilution gas chromatography-mass spectrometry. Three different doses of prostaglandin I2 were infused intravenously into conscious dogs and the effects on systemic and renal haemodynamics and urinary sodium excretion were observed. The two highest infusion rates of prostaglandin I2 (15 and 30 ng min-1 kg-1 body weight) induced significant decreases in systematic blood pressure and dose-related increases in sodium excretion, but no change in renal haemodynamics. There was a linear relationship between urinary excretion of 6-keto-prostaglandin F1 alpha and the rate of infusion of prostaglandin I2. The calculated basal rate of entry of prostaglandin I2 into the systematic circulation in conscious dogs is 4 ng min-1 kg-1 body weight, which is substantially higher than that previously reported in man.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

The contribution of PGI2 to the effects of captopril in conscious dogs in differing states of sodium balance.

There is some evidence that increased prostaglandin synthesis may mediate some of the effects of the angiotensin converting enzyme inhibitor captopril. The potential role of prostaglandin (PG)I2 in this process was assessed by measurement of changes in urinary 6-keto-PGF1 alpha excretion after captopril in eight sodium replete and depleted conscious dogs. In sodium replete animals captopril induced a small decrease in blood pressure, transient increases in effective renal plasma flow and urinary 6-keto-PGF1 alpha excretion, and progressive increases in plasma renin activity (PRA) and urinary sodium excretion. By contrast, during sodium depletion captopril induced a large decrease in blood pressure, a transient increase in effective renal plasma flow and urinary 6-keto-PGF1 alpha excretion, an early large but transient increase in PRA and small progressive increase in sodium excretion. The time course of changes after captopril suggested that increased PGI2 synthesis may contribute to the transient decrease in renal vascular resistance. The increase in PRA during sodium depletion was not associated with any change in urinary 6-keto-PGF1 alpha excretion.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Comparison of high-frequency negative-pressure oscillation with conventional mechanical ventilation in normal and saline-lavaged cats.

We modified a negative-pressure respirator to produce high-frequency, subatmospheric pressure oscillations around the chest. The effects of negative-pressure oscillation (NPO) on gas exchange, lung volume, compliance and cardiovascular variables were compared to those of conventional intermittent positive-pressure ventilation (IPPV) at 30 breath/min, using cats with normal and surfactant-depleted lungs. For frequencies in both normal lungs (1, 3, 4, 5, and 7 Hz) and saline-lavaged lungs (3, 5, and 7 Hz), peak inflating pressures were lower during NPO. Oxygenation was similar for both modes of ventilation. In cats with normal lungs, PaCO2 was significantly lower during NPO at 3 and 4 Hz (mean 24 torr) than during IPPV (mean 30 torr); normocapnia was maintained at the other frequencies. In damaged lungs, NPO and IPPV at 3 and 5 Hz resulted in similar CO2 removal, but PaCO2 was significantly higher during NPO at 7 Hz. Oscillatory tidal volumes decreased with increasing frequencies: in normal lungs, mean oscillatory tidal volume was 4.4 ml/kg at 1 Hz and 2.3 ml/kg at 7 Hz; in damaged lungs it was 6.5 ml/kg at 3 Hz and 3.2 ml/kg at 7 Hz. At 3 Hz and above, NPO was associated with a larger functional residual capacity than during sequences of IPPV matched for end-expiratory transthoracic pressure. There were no significant differences in respiratory system compliance, cardiac output, and pulmonary vascular resistance between both modes of ventilation. Further studies are warranted to investigate the potential clinical usefulness of NPO.

Animals↗
PubMed1986

Validation of a compact system for measuring gas exchange.

Measuring gas exchange in critically ill patients can provide valuable information on their nutritional status and energy expenditure. Several semiautomated machines are available for measuring oxygen consumption (VO2) and carbon dioxide production (VCO2). This study evaluated, under controlled laboratory conditions, a Gould 9000 IV prototype designed for use with mechanically ventilated patients. Various VO2 and VCO2 values were simulated at different combinations of frequency, tidal volume, minute ventilation, and inspired oxygen fraction (FIO2). Variations in frequency, tidal volume, and minute ventilation had no significant effect on the measured VO2 and VCO2, but FIO2 had a dramatic effect on the accuracy of VO2. Errors in measured VO2 were 2.6%, 3.5%, 5.9%, and 16.9% at FIO2 values of 0.22, 0.40, 0.60, and 0.80, respectively. Addition of a dead space to the spirometer dump port (to prevent room-air contamination) corrected a larger error initially found. The accuracy of VCO2 was +/- 2.6%.

Carbon Dioxide↗
PubMed1986

Regulation of the accumulation of mRNA for alpha-amylase in barley aleurone.

The effect of gibberellic acid and Ca(2+) on the accumulation of alpha-amylase mRNAs in aleurone layers of barley (Hordeum vulgare L. cv Himalaya) was studied using cDNA clones containing sequences of mRNAs for the high and low isoelectric point (pI) alpha-amylases. There is no significant hybridization between the two alpha-amylase cDNA clones under the hybridization and washing conditions employed. These clones were therefore used to monitor levels of mRNAs for high and low pI alpha-amylases. It is shown that although the synthesis of the high pI alpha-amylase proteins depends on the presence of Ca(2+) in the incubation medium, the accumulation of mRNA for this group occurs to the same degree in the presence or the absence of Ca(2+). The accumulation of low pI alpha-amylase mRNA is also not affected by the presence or absence of Ca(2+) in the incubation medium. These results establish gibberellic acid, not Ca(2+), as the principal regulator of alpha-amylase mRNA accumulation in barley aleurone, while Ca(2+) controls high pI alpha-amylase synthesis at a later step in the biosynthetic pathway.

Journal Article↗
PubMed1986

Ca-stimulated secretion of alpha-amylase during development in barley aleurone protoplasts.

The effects of gibberellic acid (GA(3)) and Ca(2+) on the synthesis and secretion of alpha-amylase from protoplasts of barley (Hordeum vulgare L. cv Himalaya) aleurone were studied. Protoplasts undergo dramatic morphological changes whether or not the incubation medium contains GA(3), CaCl(2), or both. Incubation of protoplasts in medium containing both GA(3) and Ca(2+), however, causes an increase in the alpha-amylase activity of both incubation medium and tissue extract relative to controls incubated in GA(3) or Ca(2+) alone. Isoelectric focusing shows that adding Ca(2+) to incubation media containing GA(3) increases the levels of alpha-amylase isozymes having high isoelectric points (pI). In the presence of GA(3) alone, only isozymes with low pIs accumulate. The increase in alpha-amylase activity in the incubation medium begins after 36 hours of incubation, and secretion is complete after about 72 hours. Protoplasts require continuous exposure to Ca(2+) to maintain elevated levels of alpha-amylase release. Immunoelectrophoresis shows that Ca(2+) stimulates the release of low-pI alpha-amylase isozymes by 3-fold and high-pI isozymes by 30-fold over controls incubated in GA(3) alone. Immunochemical data also show that the half-maximum concentration for this response is between 5 and 10 millimolar CaCl(2). The response is not specific for Ca(2+) since Sr(2+) can substitute, although less effectively than Ca(2+). Pulse-labeling experiments show that alpha-amylase isozymes produced by aleurone protoplasts in response to GA(3) and Ca(2+) are newly synthesized. The effects of Ca(2+) on the process of enzyme synthesis and secretion is not mediated via an effect of this ion on alpha-amylase stability or on protoplast viability. We conclude that Ca(2+) directly affects the process of enzyme synthesis and transport. Experiments with protoplasts also argue against the direct involvement of the cell wall in Ca(2+)-stimulated enzyme release.

Journal Article↗
PubMed1986

Precise dermal damage with an infrared coagulator.

Using an infrared coagulator, we have shown, in pigskin, a direct relationship between depth of injury and the duration of infra-red pulses, which was highly reproducible at a particular site. This has been related to the clinical results achieved in one patient whose three tattoos were treated with different pulse times.

Adult↗
PubMed1986

Prostaglandin E receptor subtypes in smooth muscle: agonist activities of stable prostacyclin analogues.

The agonist activities of a range of prostaglandin analogues on smooth muscle preparations sensitive to prostaglandin E2 (PGE2) have been investigated. When necessary thromboxane-like activity was eliminated using the thromboxane receptor antagonists EP 045 and EP 092. On the bullock iris sphincter, rat stomach fundus and guinea-pig trachea, (+/-) omega-tetranor-16-p-chlorophenoxy PGE2 (ICI 80205) and 16,16-dimethyl PGE2 were more active contractile agents than PGE2, whereas for relaxant activity on the cat trachea, guinea-pig trachea and dog hind limb arterial vessels in vivo the order of potency was reversed. 11-Deoxy PGE1 exhibited greater relaxant than contractile activity when compared to PGE2. Iloprost and 6a-carba-delta 6,6aPGI1 (potent mimetics of PGI2) showed high contractile activity on the PGE-sensitive preparations. PGI2 was less active and another potent PGI2 mimetic, ZK 96480, showed only very weak activity. When tested, the dibenzoxazepines SC 19220 and SC 25191 blocked the contractile actions of iloprost and 6a-carba-delta 6,6aPGI1 and those of PGE2 and 16,16-dimethyl PGE2 to similar extents. Each of the PGI2 analogues showed weak activity on the relaxant systems. On the proximal portion of the ascending colon of the rat, PGI2, iloprost, 6a-carba-delta 6,6aPGI1 and ZK 96480 always inhibited spontaneous activity at nanomolar concentrations. PGE2 and PGE1 showed weak contractile activity. The distal portion of the ascending colon was more responsive to the contractile action of PGE analogues: both iloprost and 6a-carba-delta 6,6aPGI1 showed evidence of contractile activity, whereas PGI2 and ZK 96480 always inhibited spontaneous activity. Evidence was obtained that the rat stomach fundus also contains a PGF receptor; (+/-) omega-tetranor-16-m-trifluoromethylphenoxy PGF2 alpha (ICI 81008) acted as a specific agonist. PGF2 alpha and its omega-tetranor-16-p-fluorophenoxy analogue produced a higher maximum response that ICI 81008 probably due to their additional agonist action at the PGE receptor. The data support the hypothesis that there are two subtypes of the PGE receptor. ZK 96480 has minimal activity on both receptor subtypes and appears to be a highly specific PGI2 mimetic.

Animals↗
PubMed1986

Prostaglandin endoperoxide analogues which are both thromboxane receptor antagonists and prostacyclin mimetics.

Two prostaglandin endoperoxide analogues, EP 035 and EP 157, behave as specific thromboxane receptor antagonists on isolated smooth muscle preparations such as rabbit aorta, dog saphenous vein and guinea-pig trachea. However, in human platelet-rich plasma (PRP) they produce an unsurmountable block of aggregation induced by a wide range of agents (ADP, platelet-activating factor, thrombin); this inhibitory profile is typical of that seen with either prostaglandin I2 (PGI2) or PGD2. EP 035 and EP 157 induce large increases in cyclic AMP levels (up to 20 times basal) in human PRP. Simultaneous exposure to PGE1 markedly reduces their effect on cyclic AMP; exposure to PGD2 is much less effective in this respect. The adenylate cyclase inhibitor SQ 22,536 opposes the inhibitory action of EP 035, EP 157, iloprost (a stable PGI2 analogue) and PGD2 on platelet aggregation. However, the xanthone derivative AH 6809 blocks the inhibitory action of PGD2 but does not affect EP 035, EP 157 and PGI2 and its structural analogues. EP 035 and EP 157 displace [3H]-iloprost binding to the PGI2 receptor on human platelet membranes. Displacing ability is ranked as follows: iloprost greater than 6a-carba PGI2 greater than EP 157 greater than EP 035 greater than EP 164 (alpha-dinor derivative of EP 157). This order of potency is the same as that found for activation of adenylate cyclase in homogenates of washed human platelets and for inhibition of aggregation in washed human platelets. The activities of EP 035 and EP 157 were studied in two other systems containing PGI2 receptor-adenylate cyclase complexes, the NCB-20 cell line and human lung tissue. In both cases stimulation of adenylate cyclase was found but maximum rates were below that achieved with iloprost. These effects of EP 035 and EP 157 could be correlated with their abilities to displace [3H]-iloprost binding. 5 These results indicate that EP 035 and EP 157 inhibit the aggregation of human platelets by acting as agonists at the PGI2 receptor linked to adenylate cyclase. They represent a class of compound with both thromboxane receptor blocking activity and prostacyclin mimetic activity.

Adenylyl Cyclases↗
PubMed1986

Structure and relevance of the oligosaccharide hapten of Mycobacterium avium serotype 2.

The type-specific antigen of Mycobacterium avium serotype 2, the most ubiquitous of serotypes within the M. avium complex and a major cause of disseminated and localized infections, was isolated and purified. It is of the glycopeptidolipid (mycoside C) class with a characteristic oligosaccharide hapten. This was released as the oligosaccharide alditol by base-catalyzed reductive beta-elimination, and the structure was established by a combination of gas chromatography-mass spectrometry, methylation analysis, fast atom bombardment mass spectrometry, and 13C and 1H nuclear magnetic resonance as 2,3-di-O-methyl-L-fucopyranosyl-(alpha 1----3)-L-rhamnopyranosyl-(alpha 1----2)- 6-deoxytalitol. A feature of the work was the elucidation of the absolute (enantiomeric) configuration of the sugars. This same structure, in much less detail, was previously reported as the species-specific hapten of strains of Mycobacterium paratuberculosis. Thus, the work raises the intriguing possibility that some M. avium serotypes are synonymous, at least in outer cell wall anatomy, with the agent(s) of paratuberculosis (Johne's disease), an insidious disease of vast proportions in ruminants. In addition, recognition of a specific determinant will allow a precise study of the epidemiology of M. avium infections in humans and animals.

Antigens, Bacterial↗
PubMed1986

Exchange of perspectives with other health care professionals.

The time has come for the PA profession to reach out and communicate with other health care providers--with physicians, nurses, health care administrators, and other allied health professionals. In addition, PAs must encourage these providers to share their vision of tomorrow's health care delivery system and the roles that they will play with PAs. A PA educator outlines a plan for starting the process.

Interprofessional Relations↗
PubMed1986

Host-associated iron transfer factor in normal humans and patients with transfusion siderosis.

A low molecular weight iron-binding substance that promotes bacterial growth in vitro by increasing iron availability was identified in human blood and urine. Partial purification and physical characterization indicate that this factor is similar to the host-associated iron transfer factor (HAITF) previously isolated from mammalian tissue. HAITF was found to be significantly elevated in the blood of patients with thalassemia who have transfusional siderosis. The level of HAITF in the blood of these patients was also found to correlate with that of serum iron and serum glutamic-oxaloacetic transaminase (SGOT) but not with that of serum ferritin. Thus, elevated blood levels of HAITF may explain the increased susceptibility to infection seen in patients with iron overload. Its physiologic role, however, may involve the transport of iron within cells.

Aspartate Aminotransferases↗