PubMed Health⌕ Search

Biomedical subjects

D Gibson

Publications and source records attributed to D Gibson.

At least 19 recordsLinked to original sources
PubMed1992

Isolation and structure of a brain constituent that binds to the cannabinoid receptor.

Arachidonylethanolamide, an arachidonic acid derivative in porcine brain, was identified in a screen for endogenous ligands for the cannabinoid receptor. The structure of this compound, which has been named "anandamide," was determined by mass spectrometry and nuclear magnetic resonance spectroscopy and was confirmed by synthesis. Anandamide inhibited the specific binding of a radiolabeled cannabinoid probe to synaptosomal membranes in a manner typical of competitive ligands and produced a concentration-dependent inhibition of the electrically evoked twitch response to the mouse vas deferens, a characteristic effect of psychotropic cannabinoids. These properties suggest that anandamide may function as a natural ligand for the cannabinoid receptor.

Amides↗
PubMed1992

Phospholipid binding of annexin V: effects of calcium and membrane phosphatidylserine content.

We studied the binding of fluorescein-labeled annexin V (placental anticoagulant protein I) to small unilamellar phospholipid vesicles at 0.15 M ionic strength as a function of calcium concentration and membrane phosphatidylserine (PS) content. As the mole percentage of PS in the membrane increased from 10 to 50%, the stoichiometry of binding decreased hyperbolically from 1100 mol phospholipid/mol annexin V to a limiting value of 84 mol/mol for measurements made at 1.2 mM CaCl2. Over the same range of PS content, Kd remained approximately constant at 0.036 +/- 0.011 nM. A similar hyperbolic decrease in stoichiometry was observed with vesicles containing 10 or 20% PS when the calcium concentration was increased from 0.4 to 10 mM. Thus, the density of membrane binding sites is strongly dependent on the membrane PS content and calcium concentration. The effect of calcium on annexin V-membrane binding is proposed to be due to the formation of phospholipid-calcium complexes, to which the protein binds, rather than to an allosteric effect of calcium on protein-phospholipid affinity.

Annexin A5↗
PubMed1992

Progress in assessing the quality of Australian nursing home care.

This paper critically examines the clarity, practicality, desirability and validity of the 31 outcome standards that the Commonwealth Government introduced to assess quality of care in Australian nursing homes. Key features of the Australian system in an international context are its focus on outcomes, the limited number of standards used, and the comparatively subjective nature of some standards. Directors of nursing from 410 nursing homes in the Brisbane, Sydney, Melbourne and Adelaide metropolitan areas were interviewed as part of the Nursing Home Regulation in Action Project. The overwhelming majority reported the standards as clear and desirable. In the minority of cases where problems were raised, practicability was the basis for concern. A factor analysis of the ratings given by standards monitoring teams to these 410 homes failed to demonstrate redundancy across standards or grouping of standards by objectives. Nevertheless, the standards were sufficiently highly interrelated to justify summing to produce an overall compliance score. This study shows that the 31 standards hold up well under scrutiny, both from the perspectives of key actors in the monitoring process, and from a psychometric point of view.

Australia↗
PubMed1991

Preparation, characterization, and anticancer activity of a series of cis-PtCl2 complexes linked to anthraquinone intercalators.

A new series of complexes of the type cis-PtL2X2 [where L is a monodentate AQ-Y(CH2)nNH2 and L2 is a bidentate AQ-Y(CH2)nNH(CH2)2NH2; AQ = anthraquinone, X = Cl, I, Y = NH, O] in which anthraquinone intercalators are tethered to the cis-PtCl2 unit via an (aminoalkyl)amino, (oxyalkyl)amino, or polyethylene glycol (aminoethyl)amino linker chains was prepared and screened in vitro against P388 leukemia. In vivo toxicity studies were carried out on selected complexes. All complexes were characterized by means of elemental analysis, 195Pt NMR spectroscopy, and FTIR. The 1:1 Pt-intercalator complexes displayed much higher in vitro cytotoxic activities than the 1:2 Pt-intercalator complexes. The dichloride complexes were consistently more active than their diiodide counterparts. Among the 1:1 Pt-intercalator complexes those with the shorter linker chains (n = 2, 3) exhibited the highest cytotoxic activities. Three compounds, [[2-[[2-(anthraquinon-1- ylamino)ethyl]amino]ethyl]amine-N,N']dichloroplatinum(II), [[2-[[3-(anthraquinon-1-ylamino)propyl]amino]ethyl]amine- N,N']dichloroplatinum(II), and [[2-[[3-anthraquinon-1- yloxy)propyl]amino]ethyl]amine-N,N']dichloroplatinum(II), were as active in vitro as cisplatin (ED50 = 2-4 x 10(-7) M) while on a molar basis their acute in vivo toxicity was significantly lower than that of cisplatin. In vivo screening against P388 leukemia indicated that these complexes have activity comparable to cisplatin.

Animals↗
PubMed1990

Practical applications of energy dispersive X-ray microanalysis in diagnostic oral pathology.

Energy dispersive X-ray microanalysis is a powerful tool that can reveal the presence and relative quantities of elements in minute particles in biologic materials. Although this technique has been used in some aspects of dental research, it has rarely been applied to diagnostic oral pathology. The purpose of this paper is to inform practicing dentists and oral specialists about the diagnostic potential of this procedure by presenting three case reports. The first case involved the identification of flakes of a metallic material claimed by a 14-year-old girl to appear periodically between her mandibular molars. In the second case, a periodontist was spared a lawsuit when a freely mobile mass in the antrum of his patient was found to be a calcium-phosphorus compound not related to the periodontal packing that had been used. The third case involved the differential diagnosis of amalgam tattoo and graphite tattoo in a pigmented lesion of the hard palate mucosa. The results of the analyses were significant and indicate a role for this technique in the assessment of selected cases. Potential for wider use of energy dispersive X-ray microanalysis in diagnostic oral pathology exists as research progresses.

Adolescent↗
PubMed1990

Molecular structure of the complex formed between the anticancer drug cisplatin and d(pGpG): C222(1) crystal form.

The three dimensional molecular structure of the adduct formed between the anticancer drug cisplatin and a DNA dinucleotide d(pGpG) has been determined by x-ray diffraction analysis at 1.37 A resolution and refined to a final R-factor of 0.11. This structure, solved by using data from a previously reported crystal form in the space group C222(1), resembles that found in the space group P2(1)2(1)2 (Sherman, et al., Science, 230, 412-417, 1985; ibid, J. Amer. Chem. Soc. 110, 7368-7381, 1988). In both structures, four crystallographically independent cis-[Pt(NH3)2(d(pGpG]] molecules aggregate into a tetrameric cluster that is stabilized by a large number of intermolecular hydrogen bonds and base-base stacking interactions. In each molecule, the platinum atom is coordinated to the N7 atoms of two guanine bases arranged in a head-to-head orientation, resulting in a large dihedral angle between the guanines. Intermolecular guanine-guanine base pairings between different intrastrand crosslinked molecules are used extensively in the crystal lattice.

Base Composition↗
PubMed1990

Continuous wave Doppler echocardiography and coarctation of the aorta: gradients and flow patterns in the assessment of severity.

Indices of the severity of coarctation derived from non-invasive Doppler echocardiography were compared with measurements derived from cardiac catheterisation and angiography. In 24 Doppler studies from 17 children instantaneous peak systolic and diastolic gradients and time to half peak systolic and diastolic velocities were compared with the ratio of the coarctation diameter to the diameter of descending aorta at the level of diaphragm obtained from angiographic systolic frames of the aorta. A high peak systolic gradient (greater than 40 mm Hg) or long time to half peak diastolic velocity (greater than 100 ms) (that is, maintenance of flow in diastole) were both highly specific (100%) in detecting coarctation of the aorta where the angiographic ratio was less than or equal to 0.5. Diastolic measurements, however, were more sensitive (79% both for peak diastolic gradient and for time to half peak diastolic velocity) than systolic (57% for peak systolic gradient and 64% for time to half peak systolic velocity). Even higher sensitivity (93%) was obtained when the peak systolic gradient was greater than 40 mm Hg or the time to half peak diastolic velocity was greater than 100 ms. Examination by continuous wave Doppler echocardiography is an effective non-invasive method of assessing the severity of coarctation of the aorta, particularly when systolic and diastolic events are considered together. This approach overcomes the relatively low sensitivity of peak systolic gradient alone.

Aorta, Thoracic↗
PubMed1989

Phospholipid binding properties of human placental anticoagulant protein-I, a member of the lipocortin family.

Human placental anticoagulant protein-I (PAP-I) is a member of the lipocortin/calpactin/annexin family of Ca2+-dependent phospholipid binding proteins. PAP-I was labeled with fluorescein 5-isothiocyanate (1 mol/mol); this derivative had anticoagulant activity identical to the unlabeled protein and could be used to measure Ca2+-dependent binding to phospholipid vesicles through changes in fluorescence quenching. At 1.2 mM Ca2+, 0.50 M ionic strength, pH 7.4, 25 degrees C, fluorescein-labeled PAP-I bound to phospholipid vesicles containing 80% phosphatidylcholine, 20% phosphatidylserine with a Kd of 1.2 +/- 0.2 nM (mean +/- S.D.). At an ionic strength of 0.15 M, the Kd decreased to less than 0.1 nM. Prothrombin and factor Xa both competed with fluorescein-labeled PAP-I for binding to anionic phospholipid vesicles, but with affinities at least 1000-fold weaker than PAP-I. PAP-I bound only weakly (Kd greater than 2 x 10(-5) M) to neutral or anionic phospholipid monomers, and this binding was not calcium-dependent. These results show that the affinity of PAP-I for anionic phospholipid surfaces is sufficient to explain its potency as an in vitro anticoagulant.

Annexins↗
PubMed1989

Activation of the cellular Harvey ras gene in mouse skin tumors initiated with urethane.

Mouse skin tumors, benign papillomas, and squamous cell carcinomas (SCCs) were initiated by a single topical application of urethane followed by repeated promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA). Using the NIH 3T3 focus forming assay, dominant transforming activity was detected in DNA isolated from SCC samples. Rearranged and amplified copies of the c-Ha-ras gene were detected in NIH 3T3 transformant cell lines, indicating that an activated Ha-ras gene had been transferred to the NIH 3T3 recipient cells. Analysis of p21ras from the transformant cell lines suggested that the activating ras mutation was present in codon 61. Ultimately, the Ha-ras gene was shown to be activated by a specific A----T transversion at the second position of codon 61. This mutation was detected in both benign papillomas and SCCs, suggesting the activation occurred early in tumor development. The results demonstrate a highly consistent activation of the Ha-ras oncogene by a specific point mutation, suggesting a functional role for an activated ras gene in the initiation of mouse skin tumors by urethane.

Animals↗
PubMed1989

Relation of third and fourth heart sounds to blood velocity during left ventricular filling.

To investigate the relation between changes in left ventricular inflow velocity and the timing of third and fourth heart sounds, simultaneous phonocardiograms and continuous wave Doppler traces were recorded in 48 patients (aged 17-78) with heart disease and in 21 normal children. The onset of the first vibration of the third heart sound coincided with peak left ventricular inflow blood velocity to within 5 ms in all but two of the patients. The mean (SD) difference between the two events was 5 (5) ms, which did not differ significantly from zero. The relation was similar in patients with primary myocardial disease (11), and in those with valve disease (26), hypertension (five), and coronary artery disease (four). In the normal children, the mean interval was 2.5 (5) ms--not significantly different from zero. By contrast, the first deflection of the fourth heart sound consistently preceded the timing of peak atrial inflow velocity by 55 (10) ms. Agreement was much closer between the onset of atrial flow and the onset of the atrial sound (mean difference 1 (5) ms, not significantly different from zero). Gallop sounds seem to be closely related to changes in ventricular inflow velocity, and thus to the effects of forces acting on blood flow. The forces underlying the third sound seem to arise within the ventricle and are responsible for sudden deceleration of flow during rapid ventricular filling. The fourth sound, occurring at the onset of the "a" wave, is more likely to arise from dissipation of forces causing acceleration of blood flow--that is, atrial systole itself.

Adolescent↗
PubMed1989

Decrease in plasma prostaglandin E2 is not essential for the establishment of continuous breathing at birth in sheep.

Depression of prostanoid concentrations by indomethacin induces continuous breathing in fetal sheep, but it is not known whether this is associated with changes in fetal behaviour. Furthermore, the relationship between changes in prostaglandin E2 (PGE2) concentration after delivery and the appearance of continuous breathing has not been examined. We hypothesized that the decrease in fetal PGE2 by infusion of indomethacin would induce continuous breathing and a change in behaviour such that the fetus should come to resemble a newborn lamb; and coinciding with the establishment of continuous breathing at birth, PGE2 concentrations would decrease to a critical level below that present in the fetus. We found that continuous breathing in fetal sheep induced by infusion of indomethacin was related to a decrease in PGE2 from 436 +/- 114 to 189 +/- 73 pg/ml (P less than 0.005) but that this was not associated with fetal wakefulness. In addition, measurements of carotid arterial PGE2 concentrations showed that the beginning of continuous breathing after birth occurred at a plasma concentration of PGE2 of 1245 +/- 260 pg/ml, a value about three times higher than the 422 +/- 53 pg/ml measured in the fetus during breathing activity. Together these findings suggest that PGE2 is not primarily involved in the establishment of continuous breathing at birth.

Animals↗