Biomedical subjects
Publications and source records attributed to A Taylor.
A study of 22 patients with a history or either transient ischaemic attacks or of one or more cerebrovascular accidents failed to show any relationship between circulating lipids and cerebrovascular disease.
The nuclei of Xenopus laevis oocytes contain kinases capable of phosphorylating endogenous and exogenous proteins using either ATP or GTP as phosphoryl donors. These enzymes are much more active with casein and phosvitin as substrates than with histones or protamines. The protein phosphorylating activity of oocyte nuclear extracts is not regulated by cyclic nucleotides, phorbol esters, calmodulin and calcium, or phospholipids. However, the casein phosphorylating activity can be greatly enhanced by the polyamines spermine or spermidine and drastically inhibited by heparin. Fractionation of the nuclear casein kinase activities by DEAE-Sephadex chromatography and glycerol gradient centrifugation indicate that the nuclei contain enzymes with the properties of casein kinases I and II as characterized in other species. Oocyte casein kinase I (Mr 37,000) is specific for ATP as phosphoryl donor, is only slightly inhibited by 10 micrograms/ml heparin, and is not significantly stimulated by polyamines. Casein kinase II (Mr 135,000) can use both ATP and GTP as substrates, and is very sensitive to heparin inhibition and polyamine stimulation. The fact that low concentrations of heparin (10 micrograms/ml) can inhibit a large percentage of the endogenous phosphorylation of nuclear extracts or of whole nuclei indicates that casein kinase II is probably the major protein phosphorylating activity of these oocyte organelles.
Our purpose in conducting this study was to evaluate the efficacy of an 111In-labeled murine monoclonal antibody directed against a high-molecular-weight glycoprotein in localizing metastatic melanoma in 15 patients with previously documented disease and to determine the effect of antibody mass (2.5, 5.0, and 10.0 mg) on blood clearance, biodistribution, and lesion detection. Five mCi of 111In-antibody were infused over 1 hour, and patients were scanned at 24 and 72 hours after injection without computer enhancement or background subtraction techniques. No significant differences in the organ distribution, urine excretion, or plasma disappearance curves were noted at the three antibody dose levels. There were no acute reactions. The scan detected tumor in 9 of 12 (75%) patients with active disease, and 26 of 33 (79%) lesions greater than 1 cm. Patient management in 3 of 15 (20%) of patients studied was changed as a result.
Using exogenous 125I-ubiquitin, ubiquitin-lens protein conjugation was observed with supernatants of cultured rabbit lens epithelial cells and lens cortex tissue. Conjugation was ATP-dependent with the greatest variety and amount of conjugates larger than 150 kDa. In vivo production of ubiquitin-protein conjugates in cultured rabbit and beef lens epithelial cells and rabbit lens tissues of different developmental age was established using immunological detection. There were limited similarities between conjugates found in youngest as opposed to oldest tissue. Cultured rabbit cells contained 27 pmol/mg free ubiquitin and 18 pmol/mg conjugated ubiquitin. Levels of free ubiquitin in lens tissue epithelium, cortex, and core were 36, 5, and 5 pmol/mg, respectively. There were only 2 pmol/mg conjugated ubiquitin in each of these tissues. Hydrolysis of 125I-ubiquitin was catalyzed by supernatants of cultured lens cells, beef and human lens tissues, and reticulocytes. Degradation was greatest in epithelial tissues, and least in core. This corroborates studies which show that proteolytic capabilities are attenuated in older tissue. Decreased initiation of proteolysis by ubiquitination as well as diminished proteolysis in older lens tissue may be related to the accumulation of damaged proteins in aging lens tissue.
We describe the molecular cloning and characterization of a secreted, acidic, cysteine-rich glycoprotein (SPARC) of apparent Mr 43,000 which is a major product of mouse embryo parietal endoderm. These cells are specialized for the synthesis of a rapidly expanding basement membrane, but SPARC is not itself an integral matrix component. We show that SPARC is related structurally and antigenically to an Mr 43,000 glycoprotein secreted in large amounts by bovine aortic endothelial cells as part of a 'culture shock' response to in vitro conditions promoting their proliferation and migration.
Large accumulations of postsynthetically oxidized proteins are observed in the aged and cataractous eye lens. Ascorbate has previously been used to delay photooxidative damage in vitro. The goals of this study were to confirm that dietary ascorbate can be used to enhance lens ascorbate levels and to determine if lenses with enhanced ascorbate can better withstand photooxidative stress in the form of ultraviolet (UV) light exposure. Guinea pigs were placed on high dietary ascorbate (HDA), 50 mg/day, and low dietary ascorbate (LDA), 2 mg/day, for 21 weeks. Lenses from HDA animals were found to contain 3.3 times more ascorbate than LDA animals. Prior to irradiation, SDS-PAGE protein profiles and exopeptidase activity in HDA and LDA lens soluble proteins were indistinguishable. However upon exposure to UV light, more protein damage (e.g., high-molecular-weight aggregates and enhanced loss of exopeptidase activity) was seen in lens preparations from LDA as compared to HDA animals. These results suggest that ascorbate protects lens components against cataract-like and age-related postsynthetic changes in vivo. As in previous tests on lens preparations, attenuated exopeptidase activity was observed before protein aggregation.
The murine pre-B leukemic cell line 70Z/3 contains both an unrearranged immunoglobulin kappa-light-chain gene and a functionally rearranged but silent kappa-light-chain gene. Mitogenic stimulation of growing 70Z/3 cells with bacterial lipopolysaccharide (LPS) activates kappa-light-gene transcription and results in a 10- to 20-fold increase in cytoplasmic kappa-light-chain mRNA. The induction of kappa gene expression by LPS was probed by using an inhibitor of protein synthesis. Concomitant treatment of 70Z/3 cells with LPS and cycloheximide failed to block kappa-light-chain mRNA accumulation, indicating that new protein synthesis is not required for the activation of kappa-gene expression. Treatment of 70Z/3 cells with cycloheximide alone resulted in kappa-mRNA induction equivalent to those produced by LPS alone. The kappa mRNA synthesized in the presence of cycloheximide was intact and able to direct the synthesis of kappa light chains. Nuclear transcription assays revealed that cycloheximide, like LPS, activated kappa-gene transcription. These findings indicate that the trans-acting factors necessary for kappa-light-chain-gene transcription are present in pre-B cells, but their activity is blocked by short-lived inhibitory proteins.
In order to assess the interaction between halothane and verapamil on the cardiovascular system, mongrel dogs were instrumented so that the following measurements could be made awake and under the influence of the drugs: aortic, left ventricular, and left atrial blood pressures; myocardial segment length shortening; heart rate and rhythm; and coronary, carotid, and renal blood flows. The effect of two infusion doses of verapamil (3 micrograms X kg-1 X min-1 and 6 micrograms X kg-1 X min-1 after 200 micrograms X kg-1 bolus) were examined awake. On a different day in the same dogs, two concentrations of halothane (1.2-low and 2.4-high % end-tidal) and the effect of the two infusion doses of verapamil during low and high halothane were studied. Thirty minutes of either infusion dose of verapamil produced only heart rate and electrocardiographic P-R interval increases in conscious dogs. Halothane produced dose-related decreases in mean aortic pressure, left ventricular maximum rate of tension development (dP/dt), and segment length shortening and increases in heart rate and left atrial pressure. Carotid blood flow was increased by low halothane concentrations and returned to control with high halothane concentrations. There were no significant changes in coronary or renal blood flow produced by halothane. Verapamil infusion during low halothane concentration produced minimal effects. However, both the 3 and 6 micrograms X kg-1 X min-1 verapamil doses further depressed hearts already depressed by the high concentrations of halothane and decreased renal and carotid blood flows.(ABSTRACT TRUNCATED AT 250 WORDS)
The effects of enflurane and isoflurane on the cardiovascular system and cellular calcium kinetics are somewhat different. Consequently, the interaction with the calcium channel blocking drug, verapamil, may also differ. In order to compare the anesthetics, the authors studied the effects of two infusion doses of verapamil (which produced plasma levels of 90 and 180 ng X ml-1) on cardiovascular dynamics and regional blood flow in awake dogs. On two other days, in the same dogs, the effects of approximately 1.1 and 2 MAC enflurane and isoflurane were first studied and then the same verapamil dose regimens while the same anesthetic concentrations were maintained. Verapamil produced only increases in heart rate and the P-R interval in the awake animal. The high dose of both anesthetics markedly decreased mean aortic pressure and left ventricular rate of tension development (dP/dt), and increased heart rate. However, only enflurane also decreased myocardial segment length shortening and increased left atrial pressure. Neither anesthetic alone affected coronary or renal blood flow, while both increased carotid blood flow at the low dose. Verapamil infusion during 1.2 MAC enflurane was more depressant than during 1.2 MAC isoflurane, but the combination of verapamil with 2 MAC concentration of both anesthetics was equally depressant. Both doses of both anesthetics increased plasma verapamil levels compared with the same verapamil dosing regimen awake. When these results are compared with those previously reported for halothane, the effects of verapamil during all three anesthetics are more similar than different.(ABSTRACT TRUNCATED AT 250 WORDS)
The relative renal uptake of Tc-99m DMSA was compared with the relative glomerular filtration rate (GFR) in ten patients with serum creatinines ranging from 0.3 to 2.5 mg/dl. Relative GFR was based on the renal uptake of Tc-99m DTPA determined by two methods: 1) integrating the counts from 1 to 3 minutes postinjection and correcting for background. 2) Totalizing the individual renal counts in a single 15-second frame from 2:45 minutes to 3:00 minutes postinjection and correcting for background. The two methods of determining relative DTPA uptake showed excellent correlation, r = 0.98. Relative DMSA uptake determined at 24 hours post-injection using computer-assisted regions of interest showed excellent correlation with the relative GFR determined by either the integral or single-frame method, r = 0.98. The addition of background subtraction for the DMSA images at 24 hours did not improve the correlation.
Forty patients (43 studies) referred for determination of differential renal function were imaged 24 hours after intravenous administration of Tc-99m-2, 3 DMSA. Visual assessment of relative renal uptake was estimated independently by three observers at three different hospitals from analog images on standard x-ray film. The results were compared with the relative DMSA uptake obtained by summing counts in computer-assisted regions of interest placed over each kidney. There was excellent correlation between the visual estimates of each observer and the computer-generated values (r = 0.98, 0.96, and 0.98, respectively). If a computer is not available, good visual estimates of differential uptake still may be obtained when static imaging agents such as DMSA are administered.
Functional liver blood flow and hepatic artery flow were measured before and after either end-to-side portacaval or side-to-side mesocaval shunting in dogs. Functional liver blood fell by approximately 50% following both portacaval and mesocaval shunting. The hepatic artery response was variable after both portacaval and mesocaval shunts. It is concluded that side-to-side mesocaval shunts do not preserve hepatic blood flow or produce a greater compensatory increase in hepatic artery flow than conventional portacaval shunts.
3-(3'-Isocyanocyclopent-2-enylidene)propionic acid at a concentration of 2 to 5 mug ml inhibited cellulose digestion by a mixed culture of rumen microorganisms and in other experiments inhibited the degradation of timothy hay (Phleum pratense) in a digestibility test. At isocyanide concentrations of 12 mug ml the fermentation activity of rumen fluid, measured by its dehydrogenase activity, was inhibited but not abolished. All of these isocyanide effects were reversed by the incorporation of nickelous ion into the solutions of the systems under study. The activity of 1 mol of isocyanide is reversed by about 1 mol of Ni and, in the case of the cellulose digestion test, by about 1 mol of Co. Of some 15 other ions tested only Pd and possibly chromium reversed the effect of the isocyanide.
The prognosis of patients with acute myocardial infarction is related to the infarction size. We evaluated the ability of a clinical technique, two-dimensional echocardiography, to assess infarct size based on the extent of regional contraction abnormalities. Conscious closed-chest dogs with preplaced coronary snares underwent permanent coronary occlusion. The animals were studied by two-dimensional echo 20 min and 2 days after occlusion. The extent of myocardial contraction abnormalities (systolic wall thinning instead of normal systolic thickening) was correlated with the infarct size determined pathologically. Some dogs had pressure-induced left ventricular hypertrophy. Extent of regional contraction abnormalities demonstrated by two-dimensional echo correlated well with infarct size both early (20 min) (r = 0.92) and late (2 days) (r = 0.94) after permanent coronary occlusion. Dyskinesis extent modestly overestimated the infarct size. The relationship between dyskinesis and infarct size were similar in both normal and left ventricular hypertrophied hearts. We then undertook a study to assess the effects of coronary reperfusion on dyskinesis-infarct size relationships. Conscious, closed-chest dogs underwent 1-2 h of coronary occlusion followed by 2-10 days of coronary reperfusion. Significant regional dyskinesis was present after 1-2 h of occlusion and decreased by 50-60% of the occlusion value after 2 days of reperfusion without further change in extent of dyskinesis between 2 and 10 days of reperfusion. Of importance, however, was that there was no significant correlation between infarct size and extent of regional dyskinesis by two-dimensional echo after reperfusion, either after 2 days (r = 0.09) or 10 days (r = 0.29) of reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
The data obtained in this study demonstrate that the concentration of serotonin is markedly elevated (18- to 27-fold) at the site of a coronary arterial stenosis in open-chest, anesthetized dogs with cyclic flow variations. Cyclic flow variations in this experimental preparation were abolished by ketanserin, a 5-hydroxytryptamine antagonist, but serotonin concentration at the site of the coronary stenosis remained elevated. The intra-atrial administration of serotonin (0.16 to 1 mg/min) restored cyclic flow variations after they had been abolished by ketanserin. Taken together, these data suggest that serotonin may be one of the important mediators of cyclic flow variations in this experimental preparation.
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Serial measurements of copper and zinc concentrations in serum were made at 06.00, 14.00, 22.00 and again at 06.00 hours in 37 male patients with epilepsy, aged between 9 and 19 years. Anticonvulsant drugs were administered at 08.00 and 20.00 hours, and standard hospital meals were allowed at 07.30, 12.00, 16.00 and 19.00 hours. Similar to our previous results, eight patients (21.6%) had serum copper levels greater than the reference range (11.0-20.5 mumol/l) and this hypercupraemia was associated with carbamazapine and/or phenytoin medication. No diurnal variation in serum copper level was observed. Serum copper concentration had no correlation with either 24 h urinary copper excretion or serum anti-convulsant drug levels. Serum zinc concentrations were within the reference range (10-16.5 mumol/l), confirming our previous report. No relation with anti-convulsant medication or serum copper levels was found. Diurnal variations in serum zinc levels with peak and trough concentrations at 06.00 and 14.00 hours, respectively, were observed. It is proposed that these variations in serum zinc concentrations are a normal physiological process and is unlikely to be related to anti-convulsant drugs or epilepsy.
The 111In-labeled leukocyte scan is a sensitive and specific technique for the detection and localization of abscesses. However, in reviewing an unselected series of 249 scans, six (2.3%) were false-positive cases in which leukocyte uptake by tumor mimicked an abscess. This represented 12% (6/51) with known tumor at the time of imaging. Five of the cases were primary or metastatic tumors to the soft tissues; the sixth was a skeletal metastasis. The intensity of tumor activity has been characterized as mild in the few cases of leukocyte uptake reported in the literature, suggesting that the degree of uptake is helpful in distinguishing tumor from abscess. In this study, however, variable degrees of tumor-associated activity were seen ranging from mild to very intense. These findings indicate that tumor accumulates labeled leukocytes more frequently than has been previously appreciated, that primary and metastatic neoplasms involving both the soft tissues and skeleton are involved, and that the intensity of uptake is not a reliable criterion to distinguish tumor from abscess.