PubMed Health⌕ Search

Biomedical subjects

A M Shaw

Publications and source records attributed to A M Shaw.

12 recordsLinked to original sources
PubMed1997

Repeatable diffuse visual field loss in open-angle glaucoma.

PURPOSE: The authors determined the frequency of repeatable diffuse loss as the only form of visual field damage in patients with early to moderate open-angle glaucoma in a prospective follow-up study. METHODS: The study contained 113 patients (median age, 64 years; range, 17-89 years) who were tested at 6-month intervals with program 30-2 of the Humphrey Field Analyzer (Humphrey Instruments Inc., San Leandro, CA). Although the inclusion criterion for visual acuity was > or = 20/40, on entry, 94 (83.2%) patients had an acuity of > or = 20/25. Cumulative defect curves were generated for all visual fields (median per patient, 7; range, 4-9). After randomizing the order and removing all patient information, two observers independently rated each visual field as being "normal" or showing "diffuse," "localized," or "diffuse and localized" loss. We defined repeatable diffuse loss as occurring when at least two thirds of the number of fields in the follow-up were classified as "diffuse." RESULTS: Fourteen patients (12.4%) had repeatable diffuse loss according to the cumulative defect curves. After reviewing their clinical charts, we excluded six of these patients because of early lens changes despite good visual acuity and three because of a suggestion of localized loss (on pattern deviation probability plots) in addition to the predominantly diffuse loss. The remaining five (4.4%) patients had repeatable diffuse loss that was due solely to open-angle glaucoma. CONCLUSION: Although diffuse visual field loss is exaggerated by factors other than glaucoma in the majority of patients, it can occur repeatedly in a small number of patients as the only sign of visual field damage.

Adolescent↗
PubMed1997

Intra- and interrater agreement with cumulative defect curves.

PURPOSE: To examine intra- and interrater agreement when analyzing cumulative defect curves. Cumulative defect (Bebié) curves provide a graphical representation of the visual field and allow a subjective classification of diffuse and localized loss. METHODS: We used 75 Humphrey 30-2 visual field tests, randomly chosen from a database of 782 fields of 113 patients with open-angle glaucoma. Cumulative defect curves were generated and randomly arranged into five sets, with each set containing the 75 curves in a unique sequence. Five raters (two experienced and three inexperienced) rated each set and classified each curve as showing diffuse loss, localized loss, both diffuse and localized loss, or no loss. The intra- and interrater agreement in rating the curves was then analyzed. RESULTS: Intrarater agreement ranged from 73.3-88.0% for perfect rater agreement, with 5 identical ratings. Agreement for experienced versus inexperienced raters gave similar results (means: 84.0% and 77.8%, respectively, for perfect agreement). Interrater agreement for each set, evaluated by the kappa statistic, was substantial for all 5 sets (0.65-0.71). Kappa values for each set were comparable for experienced and inexperienced raters (0.72-0.83 and 0.59-0.69 respectively). CONCLUSIONS: Analyzing the nature of visual field loss using the cumulative defect curve is simple to learn and provides high intrarater agreement as well as substantial interrater agreement.

Glaucoma, Open-Angle↗
PubMed1990

Sodium-proton exchange across the apical membrane of the alveolar type II cell of the fetal sheep.

In order to detect and characterise Na(+)-H+ countertransport in the fetal lung epithelium we have studied under a variety of conditions the effect of an outward facing H+ gradient on Na+ uptake into purified apical membrane vesicles prepared from alveolar type II cells. Kinetic analysis of the data reveals both a diffusional and a saturable component of total Na+ uptake. Evidence for the presence of a Na(+)-H+ exchanger is demonstrated by (1) stimulation of Na+ uptake by proton loading of vesicles both in the presence and absence of chemical voltage clamping; (2) saturation kinetics with respect to external Na+ with a Km of 16 mM and a Vmax of 2.1 nmol/mg protein per min; (3) amiloride inhibition of Na+ uptake driven by pH gradient. We conclude that although diffusion may be the major component of total Na+ uptake at physiological external Na+ concentration, Na(+)-H+ countertransport provides a possible mechanism for the acidification of fetal lung liquid in-vivo in addition to its established role in intracellular pH and volume regulation.

Amiloride↗
PubMed1987

The role of Ca2+ in regulating the catabolism of PAF-acether (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) in rabbit platelets.

In the present study we have investigated the effect of changes in the concentration of cytosolic free Ca2+ ([Ca2+]i) on the deacetylation-reacylation of PAF-acether (alkylacetylglycerophosphocholine, alkylacetyl-GPC) by rabbit platelets. Washed platelets were incubated with alkyl[3H]acetyl-GPC ([3H]acetyl-PAF) or [3H]alkylacetyl-GPC ([3H]alkyl-PAF) and [Ca2+]i was subsequently elevated by the addition of the ionophore A23187 or thrombin. The catabolism of PAF-acether was studied by measuring the release of [3H]acetate or the formation of [3H]alkylacyl-GPC. The ionophore inhibited the release of [3H]acetate and the formation of [3H]alkylacyl-GPC with no accumulation of lyso-[3H]PAF, indicating that the deacetylation of PAF-acether was blocked. The effect of ionophore on the deacetylation of PAF-acether was parallel with the increase of [Ca2+]i and could be reversed by the addition of EGTA. In contrast with the prolonged inhibition evoked by ionophore, thrombin, which induced a transient elevation of [Ca2+]i, merely delayed the deacetylation of PAF-acether. Since intact platelets failed to convert exogenous lyso-PAF, the effect of Ca2+ on its acylation was investigated by using platelet homogenates. These experiments showed that the acylation of lyso-PAF was inhibited by the exogenously added Ca2+, with a maximum effect at 1 mM. When the formation of endogenous lyso-PAF from the labelled pool of alkylacyl-GPC was examined, a prolonged increase in the concentration of lyso-PAF with a parallel and equally prolonged decrease in the cellular level of alkylacyl-GPC were observed after the addition of ionophore to intact platelets. The addition of EGTA reversed the effect of ionophore, thus permitting reacylation of lyso-PAF. In contrast, only a transient change in the level of lyso-PAF and alkylacyl-GPC was evoked by the addition of thrombin. Therefore we conclude that the inhibitory effect of Ca2+ on the deacetylation-reacylation of PAF-acether may have an important role in the regulation of its biosynthesis.

Acetates↗
PubMed1985

Regulation of platelet cytosolic free calcium by cyclic nucleotides and protein kinase C.

PAF elicits a rapid, concentration-dependent elevation of platelet cytosolic free calcium ([Caf]), measured by quin2. Elevation of [Caf] is transient, and the rate of reversal increases with agonist concentration. Adenylate cyclase stimulants (PGI2, PGD2) and 8-bromo cAMP; a guanylate cyclase stimulant (sodium nitroprusside) and 8-bromo cGMP; and a protein kinase C stimulant (phorbol myristate acetate) block the elevation of [Caf] induced by PAF, and accelerate its reversal. These results suggest that cAMP, cGMP and 1,2-diacylglycerol (DAG) could act as second messengers to regulate [Caf] in platelets. As PAF is known to stimulate platelet phosphoinositide hydrolysis (ergo DAG formation) but fails to elevate platelet cAMP or cGMP, it is proposed that DAG, via activation of protein kinase C, may act as an endogenous modulator of platelet [Caf]: an action that contributes to the role of DAG as a bi-directional regulator of platelet reactivity.

Aminoquinolines↗
PubMed1985

Endogenous and pharmacological mechanisms for the regulation of human platelet cytosolic free Ca2+.

Because they inhibit the processes that promote elevation of [Ca2+]i and augment the processes that promote removal of Ca2+ from the cytosol, receptor antagonists, agents that mimic or elevate cAMP, cGMP or 1,2-Diacylglycerol (DG), and both inorganic and organic Ca2+ channel blockers can be considered to act as 'Ca2+ antagonists' on human platelets. Agonist-induced elevation of [Ca2+]i is associated with phosphoinositide hydrolysis. Unlike agents that mimic or elevate cAMP, cGMP or DG, receptor antagonists and organic Ca2+ influx, mobilisation of internal Ca2+ and inositol lipid hydrolysis. Lanthanides apparently inhibit only Ca2+ influx. Thus La3+ but not Verapamil or Diltiazem block receptor-operated Ca2+ channels on human platelets. The endogenous processes that promote extrusion or sequestration of cytosolic Ca2+ may be augmented by cAMP, cGMP, DG and by Ca2+. DG, via activation of protein kinase C, may serve as a bi-directional regulator of platelet reactivity.

Aminoquinolines↗
PubMed1983

Phospholipid-induced human platelet activation: effects of calcium channel blockers and calcium chelators.

Human platelet activation (aggregation, [14C]-5HT release and TxB2 production) induced by the phospholipids, PAF and lysophosphatidic acid (LPA) was inhibited by EGTA, TMB-8 (an intracellular calcium antagonist) and by phenylalkylamine (Class II) but not 1,4-dihydropyridine (Class I) calcium channel blockers. Primary aggregation induced by PAF was selectively inhibited by phenylalkylamine (verapamil, methoxyverapamil) calcium channel blockers. Phospholipid-induced human platelet activation depends predominantly on the influx of extracellular calcium, possibly via specific receptor-operated calcium channels.

Biological Transport↗
PubMedDate not supplied

Platelet activation--a role for a 40K anti-phospholipase A2 protein indistinguishable from lipocortin.

Stimulus-response (S-R) coupling in platelets requires an intermediary other than an elevation in cytosolic free calcium ([Ca2+]i). While an increase in [Ca2+]i is essential in S-R coupling, effecting phosphorylation of myosin of relative molecular mass (Mr) 20,000 (20 K), platelet activation is also associated with phosphorylation of a 40K protein, which can occur in the absence of changes in [Ca2+]i. The 40K protein is the substrate for protein kinase C (PKC). Mounting evidence suggests that activation of PKC by diacylglycerol is the other signal involved in S-R coupling. Although phosphorylation of the 40K protein is associated with certain platelet functional responses, no precise role has been accredited to it. Recently, we and others have described several proteins (collectively known as lipocortin) which inhibit phospholipase A2 (PLA2). One of the most conspicuous proteins of this group is a 40K peptide whose inhibitory activity can be suppressed by prior phosphorylation. We hypothesized that the 40K protein described in platelets may possess anti-PLA2 activity and that phosphorylation by PKC, suppressing its inhibitory activity, may represent the mechanism underlying mobilization of arachidonic acid, the precursor of prostaglandins. The results of the present study strongly support this hypothesis.

Alkaline Phosphatase↗