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J J Walker

Publications and source records attributed to J J Walker.

At least 127 records · Page 7Linked to original sources
PubMed1989

Ontogenesis of enkephalinergic afferent systems in the opossum cerebellum.

Enkephalin (ENK) immunoreactive climbing fibers, mossy fibers and a beaded plexus of axons are present in the adult opossum's cerebellar cortex. We have used the indirect antibody peroxidase-antiperoxidase technique to study the ontogeny of enkephalinergic axons in the cerebellum of pouch young opossums from postnatal day (PD) 1 to PD 83. On PD 1, ENK axons are present in the intermediate layer of the cerebellar anlage. At PD 18, after a period of 'waiting', ENK fibers form clusters throughout the cerebellar cortex primarily within the nascent Purkinje cell layer. By PD 40, axon terminals with a climbing fiber phenotype circumscribe Purkinje cells; immature mossy fiber rosettes are present within the internal granule cell layer. A third axon phenotype, beaded ENK fibers can be distinguished on PD 68. Between PD 40 and PD 68, the distributions of ENK climbing and mossy fibers overlap in vermal lobules II-VIII and X, whereas in the hemispheres climbing fibers predominate. However, by PD 83, ENK positive climbing fibers are no longer evident in lateral folia. These results indicate that early arriving ENK axons are present before the differentiation of their cellular targets. Further, a transient appearance of ENK in discrete populations of developing climbing fibers suggests several developmental events: (1) cell death in the inferior olive, (2) collateral regression, or (3) a transient expression of this peptide, that may be characteristic of this chemically defined system of axons.

Aging↗
PubMed1989

Can platelet volume predict progressive hypertensive disease in pregnancy?

Increase in platelet size has been found in conditions with increased platelet destruction and use. This increase in platelet size can be found in patients with moderate or severe hypertension in pregnancy, even in the presence of a normal platelet count. The goal of this study was to investigate whether an increase in platelet size was present before the manifestation of the disease and therefore could be used to predict the progression of the disease before it is clinically apparent. Three hundred normal primigravid pregnancies were studied between 28 and 30 weeks' gestation, and blood was taken to assess platelet count and mean platelet volume. Two hundred sixteen patients had no hypertensive problems during their pregnancy, 84 developed hypertension, 62 had mild hypertension only with diastolic blood pressures between 90 and 99 mm Hg, 13 had moderate hypertension with diastolic blood pressures between 100 and 109, and nine had severe hypertension with diastolic blood pressure above 110. No difference was found between these groups in the parameters measured. Therefore it was felt that platelet volume may not be a useful screening test in a low-risk population. A second study was carried out to investigate the serial changes in these parameters in patients at risk of progressive disease. Thirty-four patients with essential hypertension were followed from 24 weeks with serial blood sampling to study changes in platelet size. An additional 40 patients with mild pregnancy-induced hypertension were also studied. From these patient groups, 20 patients developed severe hypertension. The mean platelet volume increased significantly at least 1 week before the hypertension became clinically apparent. There was no change in platelet count at this time. It is concluded that increasing platelet size can predict which patients are likely to progress to severe disease before it becomes clinically obvious.

Blood Platelets↗
PubMed1989

pH gradient-stimulated phosphate transport in outer medullary brush-border membranes.

Phosphate transport was studied in brush-border membrane vesicles prepared from outer medullary tissue of the porcine kidney. Phosphate uptake studies were performed in the absence of sodium at 21 degrees C. A 1.2- to 12-fold overshoot, above equilibrium values, was present with intracellular pH (pHin) equal to 8.0 and extracellular pH (pHout) equal to 6.5, which was not evident at pHin = pHout. Concentration-dependence of the pH-stimulate uptake was determined by the difference of uptake in the absence of a pH gradient (pHin = pHout) from that in the presence of a pH gradient over a large range of phosphate concentrations. The uptake was consistent with a single facilitative system characterized by apparent kinetic parameters; with Michaelis constant 149 +/- 11 microM and maximal velocity 4.9 +/- 0.4 nmol.mg protein-1.min-1, n = 3. Phosphate uptake was inhibited by the stilbene derivative 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid with a mean inhibition constant (Ki) value of 0.15 mM (n = 2). In addition, pH gradient-stimulated phosphate uptake was sensitive to furosemide and bumetanide; Ki values of 0.50 +/- 0.05 and 0.11 +/- 0.04 mM, respectively. Arsenate (1 mM) and phosphonoformate (1 mM) inhibited pH-dependent phosphate uptake, whereas sulfate (5 mM), bicarbonate (25 mM), and chloride (100 mM) were without effect, indicating that the transport system is relatively specific to phosphate and its close analogues. pH gradient-stimulated phosphate uptake was not influenced by potassium-diffusional gradients. The data provide evidence for a facilitative process in brush-border membrane vesicles isolated from outer medullary tissue of the pig kidney that is capable of transporting phosphate in the absence of sodium.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1988

Brainstem origin of serotonin- and enkephalin-immunoreactive afferents to the opossum's cerebellum.

Previous studies have described the distribution of serotonin- and enkephalin-immunoreactive elements in the posterior lobe vermis of the opossum's cerebellum. In the present study we have used a double labeling paradigm which combines the retrograde transport of horseradish peroxidase (HRP) with serotonin and enkephalin immunohistochemistry to determine the brainstem origin of serotoninergic and enkephalinergic neurons that project to the opossum's cerebellar cortex. Subsequent to HRP injections into the posterior lobe vermis, widespread areas of the medulla and pons were found to contain retrogradely labeled neurons. Serotonin-immunoreactive somata are present primarily in the raphe nuclei and the adjacent reticular formation. Enkephalinergic neurons were numerous in the raphe nuclei, medial accessory olive, gigantocellular reticular formation, locus coeruleus, and the nucleus of the trapezoid body. However, serotoninergic neurons that project to the cerebellum were located only in the medullary pyramids and the reticular formation adjacent to the raphe. Double-labeled enkephalinergic neurons were located 1) within the medullary pyramids, 2) throughout the extent of the caudal medial accessory olive, 3) in the rostral subnucleus a of the medial accessory olive, 4) in the nucleus reticularis gigantocellularis pars ventralis, 5) in the nucleus reticularis lateralis, and 6) in the nucleus reticularis ventralis lateral to the inferior olivary complex. These results indicate that although neurons containing serotonin and enkephalin immunoreactivity may be present in some of the same pontine and medullary nuclei, those serotoninergic and enkephalinergic neurons that project to the cerebellum are present primarily in restricted and spatially separate regions of the caudal medulla.

Animals↗
PubMed1988

The transfer of ketorolac tromethamine from maternal to foetal blood.

Thirty two women who were participating in an efficacy study comparing 10 mg ketorolac with 50 mg or 100 mg of pethidine in the relief of labour pain, underwent sampling of vein blood, for determination of plasma ketorolac concentrations. The sample was withdrawn at delivery and a sample of umbilical cord blood was withdrawn at the same time. The ratio of ketorolac concentrations in the cord blood sample: the maternal venous sample were calculated and plotted against the time elapsed between drug administration and sampling. Samples for one patient, withdrawn 24 min after dosing, had ketorolac concentrations below the quantification limit. The ratios in the remaining patients were all low and showed a tendency to increase with time. The mean ratio was 0.116 with a range of 0.04 in 2 patients, at 43 min and 1 h 6 min, to 0.25 at 6 h 34 min.

Adult↗
PubMed1988

Effect of maternal ketorolac administration of platelet function in the newborn.

Ketorolac is a potent analgesic agent with antiplatelet properties which is known to cross the placenta. The aim of this study was to determine whether maternal administration of ketorolac in labour had any effect on neonatal platelet function as compared with maternal administration of pethidine and prochlorperazine. Eighteen parous women were studied in labour, twelve received pethidine (control) and six received ketorolac for analgesia. Immediately after delivery, blood was taken from the umbilical vein and anticoagulated with citrate. Platelet aggregation in whole blood was studied. Ketorolac significantly inhibited aggregation in response to arachidonic acid and collagen but not ADP. These findings confirm that ketorolac crosses the placenta. The antiplatelet effects are likely to be related to ketorolac's inhibitory effect on TxA2 production which is required for arachidonic acid and collagen-induced aggregation, but not the primary aggregation response induced by ADP. These effects suggest that ketorolac should be used with caution in patients whose neonates are at risk of haemostatic problems.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1988

Screening of drugs for rapid activity against Trypanosoma cruzi trypomastigotes in vitro.

Previous studies to find drugs with an existing product licence which were active at 4 degrees C within 24 hours and which would be suitable to prevent the transmission of Chagas' disease during blood transfusion were unsuccessful. As part of an alternative approach to identify drugs active at 37 degrees C or 25 degrees C within 2 hours, over 280 compounds were screened against bloodstream trypomastigotes of Trypanosoma cruzi Sonya strain in a microslide test in vitro. Although compounds from a wide range of chemical groups were tested only three polyene antibiotics showed outstanding trypanocidal activity. Amphotericin B, candicidin and trichomycin lysed all trypomastigotes at 8 X 10(-6) as determined by microscopical techniques. However, these compounds also showed toxicity to mammalian erythrocytes at the same concentration after a 24 hours incubation period. It seems unlikely that this approach will yield a candidate replacement for gentian violet.

Amphotericin B↗
PubMed1987

Plasma fibrinolysis during and after normal childbirth.

A detailed sequential study of plasma fibrinolytic components in 42 healthy women during and after childbirth showed that striking changes occurred within minutes of placental separation. Significant increases in overall fibrinolytic activity were detected 15 min after delivery. During this period statistically significant increases in tissue plasminogen activator levels were noted but were overshadowed by a dramatic decrease in the level of plasminogen activator inhibitor (PAI). A 10-fold fall in PAI was noted by days 3-5 post-partum, suggesting that the placenta is the major source of PAI detectable at the end of pregnancy and during labour. Persisting slightly elevated levels of PAI were detected for the first few days post partum. This may be due to increased production of normal 'endothelial' PAI in response to the vascular trauma incurred by placental separation, and in response to uterine vascular changes immediately post-partum.

Antigens↗
PubMed1987

Presence of multiple sodium-dependent phosphate transport processes in proximal brush-border membrane.

Renal brush-border membrane phosphate transport was studied in early and late segments of the pig proximal tubule. Vesicles were prepared from early proximal tubules (outer cortical tissue) and late proximal tubules (outer medullary tissue). Sodium-dependent phosphate uptake into brush-border membrane vesicles was determined using voltage clamp at 5-6 s, 21 degrees C. Sodium-dependent D-glucose uptake was determined to verify the cortical and medullary tissue cuts. At pH 8.0 (pHi = pHo), two sodium-dependent phosphate transport systems were evident in the early proximal tubule: a high-affinity system [Km, 0.06 +/- 0.01 mM; maximal transport activity (Vmax), 3.6 +/- 1.1 nmol X mg protein-1 X min-1] and a low-affinity system (Km, 4.11 +/- 0.02 mM; Vmax, 9.7 +/- 0.7 nmol X mg protein-1 X min-1). In the late proximal tubule at pH 8.0, only a single high-affinity transport process (Km, 0.19 +/- 0.7 mM; Vmax, 3.4 +/- 0.5 nmol X mg protein-1 X min-1) was evident. D-Glucose kinetics at pH 7.0 revealed both a high-affinity (Km, 0.55 +/- 0.09 mM) and a low-affinity (Km, 20.09 +/- 1.39 mM) system in the early proximal segment and a single high-affinity (Km, 1.27 +/- 0.36 mM) process in the late segment. These data suggest that two systems, distinct in their affinities and capacities, are involved in both D-glucose and phosphate transport across the brush-border membrane of the early proximal tubule, but that only a single high-affinity system is present in the late segment.

Animals↗
PubMed1987

An electron microscopic study of endrin induced alterations in unmyelinated fibers of mouse sciatic nerve.

This study examined the ultrastructural alterations in peripheral nerve of adult mouse following repeated sublethal exposures to endrin, a toxic chlorinated hydrocarbon which produces symptoms indicative of neuromuscular dysfunction. Male mice were given 20 daily ip injections of endrin in sesame oil (0.2 ml) in doses that increased from 1.5 mg/kg on days 0-3, to 2.0 mg/kg on days 4-11, and to 4.0 mg/kg on days 12-19. Controls were given the same intraperitoneal volume of sesame oil without endrin. Animals were sacrificed by glutaraldehyde perfusion after 4, 7, 14, and 20 days of exposure and 14 and 92 days postinjection and sciatic nerve tissue was prepared for electron microscopy. Myelinated nerve fibers, myelin and associated Schwann cells from endrin exposed animals appeared similar to those of controls and normal animals. Various morphological alterations were observed in many unmyelinated axons from endrin exposed animals. Such alterations included swelling, dissolution of microtubules and neurofilaments, the presence of unusual numbers of axoplasmic vesicles, both scattered and in packets, and less often, extreme vacuolation. In those Schwann cells associated with damaged axons the cytoplasm and the adaxonal space frequently contained vesicles, often in packets invaginating the axolemma. The results of this study indicate that repeated subacute doses of endrin can produce morphological alterations in unmyelinated peripheral nerve fibers and their associated Schwann cells without apparent damage to myelinated nerve fibers. The results are discussed relative to other studies producing similar nerve damage and to the potential mechanisms responsible for such damage.

Animals↗
PubMed1986

Inhibition of whole blood platelet aggregation by nicardipine, and synergism with prostacyclin in-vitro.

Platelets are involved in the pathogenesis of vascular disease, and calcium channel blocking agents (CCB) such as nicardipine, are being used in the treatment of such disorders. CCB's are known to have minor anti-platelet actions from studies performed in platelet rich plasma (PRP). Recently it has become possible to study platelet aggregation in whole blood. The effects of nicardipine on whole blood platelet aggregation were studied in-vitro using the Clay-Adams Ultra Flo 100 whole blood platelet counter. Nicardipine inhibited aggregation to 0.5 micrograms/ml collagen, and 0.5 mM arachidonic acid in a dose dependent manner, but had minimal effects on aggregation to 10 microM ADP. Nicardipine also acted synergistically with prostacyclin to inhibit aggregation. The effect of nicardipine on generation of PGI2 and TxA2 from whole blood was studied. Nicardipine did not affect TxA2 production, but significantly increased PGI2 production at high concentration. The effect of nicardipine on vascular PGI2 production was also assessed using umbilical artery rings, but nicardipine had no effect on PGI2 production. This study confirms that CCBs have inhibitory actions on platelet aggregation, and this may be of value in the treatment of vascular disease.

Adenosine Diphosphate↗
PubMed1986

Platelet studies in normal pregnancy and pregnancy-induced hypertension.

The platelet count does not appear to change during normal pregnancy but a rise in the mean platelet volume (MPV) and platelet distribution width was found in the third trimester in this study of 208 healthy pregnant women. Alteration of all three platelet parameters was seen following delivery in 40 women studied sequentially. Moderately severe pregnancy-induced hypertension (PIH) was associated with no alteration of platelet parameters when compared with gestation-matched controls. Platelet abnormalities in severe PIH appeared to be related to the time of presentation and may be a reflection of the rate of progression of the underlying condition.

Female↗
PubMed1985

Inhibition of platelet aggregation in whole blood by adrenoceptor antagonists.

It has recently become possible to study platelet aggregation in whole blood which may more closely resemble the in-vivo situation as the platelets are left in their natural milieu with red and white cells present which themselves can influence aggregation. The effects of 4 adrenoceptor antagonists on platelet aggregation in whole blood were studied in-vitro using the Clay-Adams Ultra Flo 100 whole blood platelet counter. Labetalol, pindolol and propranolol inhibited aggregation to 0.5 microgram/ml collagen in a dose dependent manner, and were synergistic with prostacyclin in inhibiting collagen induced aggregation. These 3 drugs also promoted reversal of aggregation induced by 10 microM ADP, but only inhibited 0.5 mM arachidonic acid induced aggregation at high drug concentrations. Atenolol had no effect on either collagen, ADP or arachidonic acid induced aggregation. The anti-platelet effect of these drugs may be of value in the treatment of vascular disease.

Adenosine Diphosphate↗