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Biomedical subjects

H E Taylor

Publications and source records attributed to H E Taylor.

At least 19 recordsLinked to original sources

Geochemistry of bed and suspended sediment in the Mississippi river system: provenance versus weathering and winnowing.

Stream-bed sediment for the size fraction less than 150 microm, examined in 14,000 samples collected mostly from minor tributaries to the major rivers throughout the Mississippi River drainage system, is composed of 5 mineral fractions identified by factor analysis-Al-silicate minerals, quartz, calcite and dolomite, heavy minerals, and an Fe-Mn fraction. The Al-silicate fraction parallels its distribution in the regolith, emphasizing the local sediment source as a primary control to its distribution. Quartz and the heavy-mineral fraction, and associated trace elements, exhibit a complementary distribution to that of the Al-silicate fraction, with a level of enrichment in the bed sediment that is achieved through winnowing and sorting. The carbonate fraction has a distribution suggesting its dissolution during transport. Trace elements partitioned onto the Fe-Mn, possibly amorphous oxyhydride, fraction are introduced to the streams, in part, through human activity. Except for the heavy-mineral fraction, these fractions are identified in suspended sediment from the Mississippi River itself. Although comparison of the tributary bed sediment with the riverine suspended sediment is problematic, the geochemistry of the suspended sediment seems to corroborate the interpretation of the geochemistry of the bed sediment.

Geologic Sediments↗

TFII-I, a candidate gene for Williams syndrome cognitive profile: parallels between regional expression in mouse brain and human phenotype.

The gene for TFII-I, a widely expressed transcription factor, has been localized to an interval of human chromosome 7q11.23 that is commonly deleted in Williams syndrome (WS). The clinical phenotype of WS includes elfin facies, infantile hypercalcemia, supravalvular aortic stenosis, hyperacusis and mental retardation. The WS cognitive profile (WSCP) is notable for the differential impairment of visual-spatial abilities with relative sparing of verbal-linguistic function. Fine mapping of individuals with WS has revealed a close association between deletion of TFII-I and the WSCP. To determine the plausibility of the hypothesis that hemizygous deletion of TFII-I contributes to the WSCP, we have examined the anatomic distribution of TFII-I RNA and protein isoforms in brains from adult and embryonic mice. Our studies show that early in development, TFII-I expression is widespread and nearly uniform throughout the brain. In adult brain, TFII-I protein is present exclusively in neurons. Highest levels of expression are observed in cerebellar Purkinje cells and in hippocampal interneurons. TFII-I immunoreactivity is distinct from that of the related protein, TFII-IRD1, which is also localized to the region of human chromosome 7 deleted in WS. The expression pattern of TFII-I in mouse brain parallels regions in human brain which have been shown to be anatomically and functionally altered in humans with WS. These observations are consistent with the hypothesis that deletion of the gene for TFII-I contributes to the cognitive impairments observed in WS.

Animals↗

Influence of natural organic matter on the adsorption of metal ions onto clay minerals.

The influence of natural organic matter (NOM) on the adsorption of Al, Fe, Zn, and Pb onto clay minerals was investigated. Adsorption experiments were carried out at pH = 5 and pH = 7 in the presence and absence of NOM. In general, the presence of NOM decreased the adsorption of metal ions onto the clay particles. Al and Fe were strongly influenced by NOM, whereas Zn and Pb adsorption was only slightly altered. The interaction of the metal ions with the minerals and the influence of NOM on this interaction was investigated by coupling SdFFF with an inductively coupled plasma mass spectrometer (ICPMS) or an inductively coupled plasma atomic emission spectrometer (ICPAES). Quantitative atomization of the clay particles in the ICP was confirmed by comparing elemental content determined by direct injection of the clay into the ICPMS with values from acid digestion. Particle sizes of the clays were found to be between 0.1 and 1 microm by sedimentation field-flow fractionation (SdFFF) with UV detection. Aggregation of particles due to metal adsorption was observed using SdFFF-ICPMS measurements. This aggregation was dependent on the specific metal ion and decreased in the presence of NOM and at higher pH value.

Adsorption↗

Distribution of inorganic mercury in Sacramento River water and suspended colloidal sediment material.

The concentration and distribution of inorganic Hg was measured using cold-vapor atomic fluorescence spectrometry in samples collected at selected sites on the Sacramento River from below Shasta Dam to Freeport, CA, at six separate times between 1996 and 1997. Dissolved (ultrafiltered, 0.005 microm equivalent pore size) Hg concentrations remained relatively constant throughout the system, ranging from the detection limit (< 0.4 ng/L) to 2.4 ng/L. Total Hg (dissolved plus colloidal suspended sediment) concentrations ranged from the detection limit at the site below Shasta Dam in September 1996 to 81 ng/L at the Colusa site in January 1997, demonstrating that colloidal sediment plays an important role in the downriver Hg transport. Sequential extractions of colloid concentrates indicate that the greatest amount of Hg associated with sediment was found in the "residual" (mineral) phase with a significant quantity also occurring in the "oxidizable" phase. Only a minor amount of Hg was observed in the "reducible" phase. Dissolved Hg loads remained constant or increased slightly in the downstream direction through the study area, whereas the total inorganic Hg load increased significantly downstream especially in the reach of the river between Bend Bridge and Colusa. Analysis of temporal variations showed that Hg loading was positively correlated to discharge.

California↗

The occurrence and distribution of selected trace elements in the Upper Rio Grande and tributaries in Colorado and northern New Mexico.

Two sampling trips were undertaken in 1994 to determine the distribution of trace elements in the Upper Rio Grande and several of its tributaries. Water discharges decreased in the main stem of the Rio Grande from June to September, whereas dissolved concentrations of trace elements generally increased. This is attributed to dilution of base flow from snowmelt runoff in the June samples. Of the three major mining districts (Creede, Summitville, and Red River) in the Upper Rio Grande drainage basin, only the Creede District appears to impact the Rio Grande in a significant manner, with both waters and sediments having elevated concentrations of some trace elements considerably downriver. For example, dissolved zinc concentrations upriver of Willow Creek, which primarily drains the Creede District, were about 2-3 microg/L; immediately downstream of the Willow Creek confluence, concentrations were above 20 microg/L; and elevated concentrations occurred in the Rio Grande for the next 100 km. The Red River District does not significantly impact the Upper Rio Grande for most trace elements. Because of current water management practices, it is difficult to assess the impact of the Summitville District on the Upper Rio Grande. There are, however, large increases in many dissolved trace element concentrations as the Rio Grande passes through the San Luis Valley, coincident with elevated concentrations of those same trace elements in tributaries. Among these elements are As, B, Cr, Li, Mn, Mo, Ni, Sr, U, and V. None of the trace elements exceeded U.S. EPA primary drinking water standards in either survey, with the exception of cadmium in Willow Creek. Secondary drinking water standards were frequently violated, especially in tributaries draining areas where mining has occurred. Dissolved zinc (in Willow Creek in both June and September) was the only element that exceeded the EPA Water Quality Criteria for aquatic life of 120 microg/L.

Animals↗

1-Alkylcarbonyloxymethyl prodrugs of 5-fluorouracil (5-FU): synthesis, physicochemical properties, and topical delivery of 5-FU.

1-Alkylcarbonyloxymethyl (1-ACOM) prodrugs of 5-fluorouracil (5-FU) have been synthesized and characterized by their solubilities in isopropyl myristate (SIPM) and pH 4.0 buffer (SH2O), by their partition coefficients between isopropyl myristate (IPM) and pH 4.0 buffer (K) and by their abilities to deliver total 5-FU species into (Cs) and through (Ji) hairless mouse skin from an IPM vehicle. All of the prodrugs were much more lipophilic (SIPM) than 5-FU (> 60 times), and two members of the series (alkyl = C1 and C2, acetyl- and propionyloxymethyl) were also more soluble in water than 5-FU. The two more water-soluble members gave larger Ji values than the other members of the series, with C2 exhibiting the best biphasic solubility and the largest Ji value (16 times that of 5-FU). The ability of the 1-ACOM-5-FU prodrugs to deliver total 5-FU species into skin (Cs) was greater than the delivery of 5-FU by 5-FU, except for the last two members of series (alkyl = C7 and C9, octanoyl- and decanoyl-oxymethyl). However, the ratios of normalized Cs to Ji for the series was less than that exhibited by 5-FU, except for C7 and C9. Also, except for C9, significant amounts of intact prodrug as percentages of total 5-FU species were found in the receptor phases during the course of the diffusion cell experiments, ranging from 55% for C1 to 12% for C7.

Administration, Cutaneous↗

Double tagging recombinant A1- and A2A-adenosine receptors with hexahistidine and the FLAG epitope. Development of an efficient generic protein purification procedure.

An expression plasmid for mammalian cells (CLDN10B) has been modified to add nucleotides encoding hexahistidine and the FLAG peptide (H/F) to cDNAs. The new mammalian expression plasmid has been named pDoubleTrouble (pDT). The plasmid and a recombinant baculovirus were used to produce native-and H/F-human A1 and A2A adenosine receptors, optimally expressed in CHO-K1 and Sf9 cells, respectively. Binding to recombinant H/F-A1 receptors (Bmax = 30 pmol/mg protein) was characterized using [3H]8-cyclopentyl-1,3-dipropylxanthine ([3H]CPX) and 125I-N6-aminobenzyladenosine (125I-ABA). Binding to H/F-A2A receptors (Bmax = 48 pmol/mg protein) was characterized using [3H]5'-N-ethylcarboxamidoadenosine ([3H]NECA) and [3H]2-[4-(2-carboxyethyl)phenethylamino]-NECA ([3H]CGS21680). By comparison to native receptors, the addition of H/F to the amino termini of these receptors had no effect on the binding affinities cyclic AMP accumulation in intact cells was not affected by the H/F extension. Anti-FLAG and Ni-nitrilotriacetic acid affinity chromatography resulted in high yield ( >50% overall recovery) of nearly homogeneous deglycosylation with N-glycosidase F. We anticipate that pDT will be generally useful for facilitating the purification in high yield of recombinant receptors and other proteins by single or sequential affinity chromatography steps.

Adenosine↗

Interventional telemedicine for noninvasive neuroradiosurgery: remote-site high-performance computing, mathematical optimization, and virtual scenario simulation.

Interventional Telemedicine may have potential utility in providing connectivity and access to specialized high performance computing and advanced software resources in support of clinical procedures in the field of Minimally-Invasive Surgery and Stereotactic Linear Accelerator (LINAC) Radiosurgery. Such interventions may benefit from application of nonlinear quadratic inverse solution methods designed to provide the capability to reverse optimize a 'best case' treatment plan. The formidable decision-making challenges posed by increasingly complex optimized data and progressively versatile LINAC delivery systems require volume visualization of projected treatment data and imaging anatomy via photorealistic rendering and virtual scenario simulation techniques. Both these new directions are heavily dependent on access to specialized high performance computing platforms solely accessible via broad-bandwidth network connectivity. This pilot project presents resimulation of retrospective radiosurgical case data using inverse solution optimization models running on workstation clusters and then volume rendered and simulated on the Princeton Graphics Engine Supercomputer. Evidence for effective utilization of such optimization and virtual simulation methods running on remotely accessed, distant high performance computing resources is discussed in view of the potential for long-term clinical investigation and eventual development of Interventional Telemedicine as a clinically practical approach for providing support to remote or non-urban radiosurgery centers in the industrialized and developing world.

Algorithms↗

A1 adenosine receptors. Two amino acids are responsible for species differences in ligand recognition.

Species differences in ligand binding to A1 adenosine receptors were localized to the seventh transmembrane (TM7) region based on the binding of [8-3H]cyclopentyl-1, 3-dipropylxanthine and three other ligands to wild type and six bovine/canine interspecies receptor chimeras expressed in COS-1 cells. Subsequent site-directed mutagenesis experiments identified amino acid 270 (isoleucine/methionine, bovine/canine) as being primarily responsible for species differences in the binding of N6-adenine-substituted compounds, R-N6-phenylisopropyladenosine (R-PIA) and (S)-N6-endonorbornan-2-yl-9-methyladenine, and the C-8-substituted xanthine, [3H]cyclopentyl-1,3-dipropylxanthine. These data are consistent with the hypothesis that the N6 region of adenines and the C-8-region of xanthines bind to the same region of the receptor. A second TM7 amino acid, 277 (serine/threonine, bovine/canine), selectively influences the binding of the ribose-substituted adenosine analog, 5'-N-ethylcarboxamidoadenosine to a variable extent, depending on the nature of amino acid 270. We hypothesize that amino acid 270 of the A1 receptor interacts with the N6 region of adenosine, while amino acid 277 is important, especially in the absence of an N6 substitution, for interactions with a distinct nucleoside region, possibly on the ribose.

Adenosine↗

Molecular cloning and characterization of the human A3 adenosine receptor.

The human A3 adenosine receptor was cloned from a striatal cDNA library using a probe derived from the homologous rat sequence. The cDNA encodes a protein of 318 amino acids and exhibits 72% and 85% overall identity with the rat and sheep A3 adenosine receptor sequences, respectively. Specific and saturable binding of the adenosine receptor agonist N6-(4-amino-3-[125I]iodobenzyl)adenosine [125I]ABA was measured on the human A3 receptor stably expressed in Chinese hamster ovary cells with a Kd = 10 nM. The potency order for adenosine receptor agonists was N-ethylcarboxamidoadenosine (NECA) > or = (R)-N6-phenyl-2-propyladenosine [(R)-PIA] > N6-cyclopentyladenosine (CPA) > (S)-N6-phenyl-2-propyladenosine [(S)-PIA]. The human receptor was blocked by xanthine antagonists, most potently by 3-(3-iodo-4-aminobenzyl)-8-(4-oxyacetate)phenyl-1-propylxanthine (I-ABOPX) with a potency order of I-ABOPX > 1,3-dipropyl-8-(4-acrylate)phenylxanthine > or = xanthine amino congener >> 1,3-dipropyl-8-cyclopentylxanthine. Adenosine, NECA, (R)- and (S)-PIA, and CPA inhibited forskolin-stimulated cAMP accumulation by 30-40% in stably transfected cells; I-ABA is a partial agonist. When measured in the presence of antagonists, the dose-response curves of NECA-induced inhibition of forskolin-stimulated cAMP accumulation were right-shifted. Antagonist potencies determined by Schild analyses correlated well with those established by competition for radioligand binding. The A3 adenosine receptor transcript is widespread and, in contrast to the A1, A2a, and A2b transcripts, the most abundant expression is found in the lung and liver. The tissue distribution of A3 mRNA is more similar to the widespread profile found in sheep than to the restricted profile found in the rat. This raises the possibility that numerous physiological effects of adenosine may be mediated by A3 adenosine receptors.

Adenosine↗

Molecular cloning and functional expression of a sheep A3 adenosine receptor with widespread tissue distribution.

Using the polymerase chain reaction, an A3 adenosine receptor has been cloned from the hypophysial par tuberalis of sheep. The clone encodes a 317-amino acid protein that is 72% identical to the rat A3 adenosine receptor. In contrast to rat, where abundant A3 mRNA transcript is found primarily in testis, the sheep transcript is most abundant in lung, spleen, and pineal gland and is present in moderate levels in brain, kidney, and testis. The agonist N6-amino[125I]iodobenzyladenosine binds with high affinity (Kd congruent to 6 nm) and specificity to recombinant A3 adenosine receptors expressed transiently in COS-1 cells or stably in CHO K1 cells. The potency order of agonists is N6-aminoiodobenzyladenosine > N-ethylcarboxamidoadenosine > or = (R)-phenylisopropyladenosine >> cyclopentyladenosine. Little or no binding of purine nucleotides was detected. The potency order of antagonists is 3-(3-iodo-4-aminobenzyl)-8-(4-oxyacetate)phenyl-1- propylxanthine (I-ABOPX) (Ki = 3 nM) > 1,3-dipropyl-8-(4-acrylate)phenylxanthine (BW-A1433) > 1,3-dipropyl-8-sulfophenylxanthine = xanthine amine cogener >> 8-cyclopentyl-1,3-dipropylxanthine. Enprofylline does not bind. These data indicate that, in contrast to A1 adenosine receptors, A3 adenosine receptors preferentially bind ligands with aryl rings in the N6-position of adenine and in the C8-position of xanthine. Among antagonists, the A3 adenosine receptor preferentially binds 8-phenylxanthines with acidic versus basic para-substituents (I-ABOPX > BW-A1433 > 1,3-dipropyl-8-sulfophenylxanthine = xanthine amine cogener). Agonists reduce forskolin-stimulated cAMP accumulation in Chinese hamster ovary cells stably transfected with recombinant sheep A3 adenosine receptors; the reduction is blocked by BW-A1433 but not by 8-cyclopentyl-1,3-dipropylxanthine. These data suggest that (i) A3 adenosine receptors display unusual structural diversity for species homologs, (ii) in contrast to rat, sheep A3 adenosine receptors have a broad tissue distribution, and (iii) some xanthines with acidic side chains bind with high affinity to A3 adenosine receptors.

Amino Acid Sequence↗

The precise radioimmunoassay of adenosine: minimization of sample collection artifacts and immunocrossreactivity.

Anti-adenosine antibodies were produced in rabbits immunized with N6-carboxymethyladenosine conjugated to methyl albumin. 125I-N6-Aminobenzyladenosine was synthesized and used as a high-specific-activity, high-affinity ligand. A radioimmunoassay (RIA) was developed that can detect 6.25 nM (312.5 fmol) of underivatized adenosine and cross-reacts less than 0.02% with adenine nucleotides and guanosine and not at all with 1 mM inosine. The sensitivity of the RIA can be increased to a detection limit of 0.125 nM (6.25 fmol) by derivitizing samples with benzyl bromide to form N6-benzyladenosine. The assay was adapted to an automated RIA procedure. Assay precision was increased by: (i) inhibiting slight adenosine deaminase activity present in anti-sera; (ii) treating buffers and albumin used in the RIA with charcoal to remove contaminating adenosine; and (iii) correcting for a small but variable component of immunoreactivity not attributable to adenosine. A second antibody prepared with a 2',3'-disuccinyladenosine-albumin conjugate was also found to detect some non-adenosine-mediated immunoreactivity in plasma samples. Immunointerference in human plasma was eliminated in samples treated with ZnSO4/Ba(OH)2 or partially purified over C18 Sep Paks to remove nucleotides and assayed after sample benzylation or succinylation. Human blood was mixed with a novel "stop" solution that was optimized to inhibit adenosine formation from AMP by greater than 99% and to inhibit adenosine uptake into red cells and degradation by greater than 94%. Human plasma/stop solution was assayed by RIA and HPLC with equivalent results.

Adenine↗

Improved detection of ischemia-induced increases in coronary sinus adenosine in patients with coronary artery disease.

Attempts to monitor coronary sinus adenosine as a clinical marker of myocardial ischemia in humans have been disappointing. Accordingly, procedures have been developed for detecting adenosine in blood collected from the human coronary sinus. Collection involves using a double-lumen metabolic catheter, which allows blood to be mixed with a stop solution at the catheter tip, thereby minimizing adenosine formation and degradation. A five-component stop solution almost completely arrests adenosine formation and degradation. Adenosine analysis is improved by using both boronate and C18 Sep-Pak columns to purify and concentrate adenosine in human plasma before HPLC. Plasma adenosine in the coronary sinus of patients with and without coronary artery disease, measured before and during peak atrial pacing, showed a twofold atrial pacing-induced increase in adenosine in the patients with coronary artery disease (n = 9, P less than 0.001) but no change in the patients with normal epicardial coronary arteries (n = 6). These preliminary results indicate that coronary sinus adenosine may provide an index of myocardial ischemia in patients with coronary artery disease.

Adenosine↗

Oral administration of BCG as an adjuvant to surgical treatment of carcinoma of the bronchus.

A controlled clinical trial of the value of bacille Calmette--Guérin (BCG) vaccine given orally to patients with resectable carcinoma of the lung was conducted in 18 centres across Canada. A total of 308 patients were included in the analysis, 155 in the BCG group and 153 in the control group. The two groups were similar at the time of admission to the trial. BCG (120 mg) was given orally at weekly intervals for 1 month, every 2 weeks up to 3 months and then every 3 months until the total duration of therapy was 18 months. Over a 3- to 5-year follow-up period after the operation there was no difference in survival between the two groups, the proportion alive at 2 years being 61% in the BCG group and 58% in the control group. There was also no evidence of differences in the time to the detection of recurrent or metastatic disease or in the distribution of such disease. An analysis of prognostic factors confirmed the poor survival associated with histologically confirmed lymph node involvement. It may be concluded that no favourable effect from the oral administration of BCG was demonstrated.

Adjuvants, Immunologic↗

Canadian clinical trial of antilymphocyte globulin in human cadaver renal transplantation.

A multicentre, randomized clinical trial of antilymphocyte globulin (ALG) was conducted among patients who had undergone cadaver kidney transplantation; follow-up was continued for a minimum of 1 year. Of the 179 patients 92 were given conventional treatment only, while 87 were given in addition ALG (from a standardized, highly immunosuppressive, common pool of equine ALG), 20 mg/kg-d intravenously for 10 days after transplantation. The ALG-treated group had better accumulated graft survival, fewer nephrectomies, better graft function, less than half the number of acute rejection episodes and less prednisone use. There was a beneficial drug (ALG)-related effect in both the graft and the host during the first 3 months after transplantation.

Antilymphocyte Serum↗