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Biomedical subjects

G E Hall

Publications and source records attributed to G E Hall.

At least 19 recordsLinked to original sources
PubMed2000

Transient laser frequency modulation spectroscopy.

Explicitly time-dependent implementations of optical frequency modulation spectroscopy have been recently applied to a wide range of problems in chemical physics. We provide a brief description of the methodology, with an emphasis on its intrinsic advantages for interrogating transient species. Several examples highlight the application of the technique to high-resolution absorption spectra of free radicals, rate measurements for gas-phase reactions, and Doppler spectroscopy of the gas-phase products of photoinitiated reactions.

Journal Article↗
PubMed1999

Characterization of randomly-obtained matrix attachment regions (MARs) from higher plants.

Matrix attachment regions (MARs) can be operationally defined as DNA fragments that bind to the nuclear matrix. We have created a library of randomly obtained MARs from tobacco (Nicotiana tobacum) by cloning DNA fragments that co-isolate with nuclear matrixes prepared by a method involving lithium diiodosalicylate. The interactions of several of the cloned MARs with nuclear matrixes were tested by an in vitro binding assay in which genomic DNA was used as competitor. Based on this assay, the MARs were classified as strong, medium, and weak binders. Examples of each of the binding classes were further studied by in vitro binding using self- and cross-competition. Estimates of dissociation constants for several MARs ranged from 6 to 11 nM and correlated inversely with binding strength. The number of binding sites per matrix for several MARs ranged from 4 x 10(5) to 9 x 10(5) and correlated directly with binding strength. We conclude that binding strength, as we have measured it, is a function of both numbers of binding sites and affinity for the sites. The tobacco MARs were sequenced and analyzed for overall AT content, for distribution of AT-rich regions, and for the abundance of several MAR-related motifs. Previously identified MAR motifs correlate to various degrees with binding strength. Notably, the Drosophila topoisomerase II motif does not correlate with binding strength of the tobacco MARs. A newly identified motif, the "90%AT Box," correlates better with binding strength than any of the previously identified motifs we investigated.

Base Sequence↗
PubMed1998

Platinum concentrations in urban road dust and soil, and in blood and urine in the United Kingdom.

Increasing Pt concentrations from vehicle catalysts have been reported from a number of countries. Analysis of Pt and Pd in soils and road dusts taken from areas of high and low traffic flows in SE England show concentrations of Pt in the range < 0.30-40.1 ng g-1 and Pd in the range < 2.1-57.9 ng g-1. Higher concentrations of Pt are associated with high traffic densities. Samples taken from streets of lower traffic flows were found to contain the lower concentrations of the ranges. Pilot studies of Pt concentrations in blood and urine using ICP-MS have been carried out. Platinum concentrations in whole blood were: precious metal workers, 780-2170, mean 1263 pmol l-1 (0.152-0.423, mean 0.246 microgram l-1); motorway maintenance workers, 645-810, mean 744 pmol l-1 (0.126-0.158, mean 0.145 microgram l-1); Imperial College staff, 590-713, mean 660 pmol l-1 (0.115-0.139, mean 0.129 microgram l-1). Platinum concentrations in urine in pmol Pt per mmol creatinine were: precious metal workers, 122-682, mean 273 [0.21-1.18, mean 0.47 microgram Pt (g creatinine)-1]; motorway maintenance workers, 13-78, mean 33.7 [0.022-0.135, mean 0.058 microgram Pt (g creatinine)-1]; Imperial College staff, 28-130, mean 65.6 [0.048-0.224, mean 0.113 microgram Pt (g creatinine)-1]. Detection limits were 0.03 microgram l-1 for both blood and urine. The possible health effects of increasing Pt in the environment are discussed. Platinum provides an excellent example of the significance of speciation in metal toxicity. Platinum allergy is confined to a small group of charged compounds that contain reactive ligand systems, the most effective of which are chloride ligand systems. Metallic Pt is considered to be biologically inert and non allergenic and since the emitted Pt is probably in the metallic or oxide form, the sensitising potential is probably very low. Platinum from road dusts, however, can be solubilised, and enter waters, sediments, soils and the food chain. There is at present no evidence for any adverse health effects from Pt in the general environment, particularly allergic reactions.

Air Pollutants↗
PubMed1997

Pharmaceutical services in the United States Navy.

The status of pharmaceutical services in the United States Navy is described. In support of operational forces, pharmacists serve on hospital ships and in tent-based-fleet hospitals. The Navy has a long-term commitment to ensuring that its pharmacists receive postgraduate education and training; each year, pharmacists are selected for specific programs. Pharmacy technicians in the Navy have considerably more responsibility than their civilian counterparts; all complete a 23-week course, and many are board certified. Increasingly, Navy pharmacists provide pharmacokinetic services, counsel patients, serve as an information resource for provides, work in pharmacist-managed clinics, develop clinical pathways, and evaluate drug therapy. Automation and computerization are viewed as answers to challenges created by continued "rightsizing" of the staff and fiscal restraints. A project is under way that will consolidate historical and current patient information for improved clinical decision-making. The scope of Navy pharmacy practice is expanding dramatically.

Automation↗
PubMed1996

Radon, fluoride and 62 elements as determined by ICP-MS in 145 Norwegian hard rock groundwater samples.

Hard rock groundwater (145) samples collected from private drinking water wells in the environs of Oslo and Bergen were analysed for their radon and fluoride contents. A further 62 elements were determined by inductively coupled plasma mass spectrometry (ICP-MS). For 59 elements, more than 50% of all concentration values were above the detection limit. Characteristic differences between the Oslo- and Bergen-dataset can be shown to be related to host rock lithology. Variation in element contents generally spans 2-6 orders of magnitude. Concentrations of several elements (e.g. Ba, F, Fe, Mn, Na, Rn) exceed current drinking water action levels in a significant number of cases. High levels of other parameters such as Be, Mo, Th and U, which could have an impact on health, were observed. There are no Norwegian action levels currently defined for these elements. The economic and toxicological impacts of these findings require urgent assessment.

Elements↗
PubMed1993

Scaffold attachment regions increase reporter gene expression in stably transformed plant cells.

The yeast ARS-1 element contains a scaffold attachment region (SAR) that we have previously shown can bind to plant nuclear scaffolds in vitro. To test effects on expression, constructs in which a chimeric beta-glucuronidase (GUS) gene was flanked by this element were delivered into tobacco suspension cells by microprojectile bombardment. In stably transformed cell lines, GUS activity averaged 12-fold higher (24-fold on a gene copy basis) for a construct containing two flanking SARs than for a control construct lacking SARs. Expression levels were not proportional to gene copy number, as would have been predicted if the element simply reduced position effect variation. Instead, the element appeared to reduce an inhibitory effect on expression in certain transformants containing multiple gene copies. The effect on expression appears to require chromosomal integration, because SAR constructs were only twofold more active than the controls in transient assays.

Base Sequence↗
PubMed1989

Parathyroid hormone alteration of free and tRNA-bound proline specific activities in cultured mouse osteoblast-like cells.

The effects of the synthetic amino-terminal fragment of parathyroid hormone [bPTH-(1-34)] on proline uptake and on the specific activities of intracellular free proline and tRNA-bound proline were studied in confluent primary cultures of osteoblast-like cells isolated from neonatal mouse calvaria. Pretreatment of cells for 4 hours with 24 nM bPTH-(1-34) increased subsequent proline uptake by approximately 50-60%; also increased were the specific activities of both intracellular free proline and tRNA-bound proline when [3H]proline was included in the extracellular uptake solution. Specific activities of the free and tRNA-bound proline pools remained elevated after proline uptake times of as long as 30 minutes and 120 minutes, respectively. These results indicate that experiments in which radiolabeled proline is used to evaluate PTH-induced protein synthesis in bone cells must be interpreted cautiously, since apparent changes in protein synthesis might actually reflect, at least in part, PTH-induced changes in the specific activities of precursor pools.

Animals↗
PubMed1987

Role of carbonic anhydrase in bone resorption: effect of acetazolamide on basal and parathyroid hormone-induced bone metabolism.

The effects of the carbonic anhydrase inhibitor acetazolamide on basal and parathyroid hormone (PTH)-induced bone metabolism were studied to evaluate the manner in which acetazolamide inhibits bone resorption. Half-calvaria from 5 to 6-day-old mice were cultured using the following treatments: control; acetazolamide (10, 33, or 100 microM); PTH (16.7 nM bovine PTH 1-34); acetazolamide + PTH. The effects of acetazolamide on PTH-induced cAMP accumulation and protein synthesis were determined. Media from bones cultured for 48 hours were analyzed for calcium to assess bone resorption, glucose to assess calvarial glucose utilization, and lactic acid to assess calvarial lactic acid release. Media were also assayed for beta-glucuronidase activity as an indicator of lysosomal enzyme release and for lactate dehydrogenase activity as an indicator of cytosolic enzyme release and cytotoxicity. Acetazolamide at 100 microM completely inhibited PTH-induced bone resorption. This inhibition did not appear to be due to cell death, as acetazolamide did not increase lactate dehydrogenase release. Acetazolamide had no effect on PTH-enhanced cAMP levels, indicating that receptor binding and adenylate cyclase activation were unaffected. Acetazolamide alone did not alter calvarial protein synthesis, but did significantly inhibit protein synthesis in the presence of PTH. PTH significantly enhanced calvarial glucose utilization, lactic acid release, and beta-glucuronidase release. Acetazolamide inhibited all of these PTH-induced parameters in a manner that roughly paralleled its inhibition of bone resorption; acetazolamide alone had no effect on the basal values. Our results indicate that acetazolamide inhibition of bone resorption in vitro may involve general alterations in hormonally stimulated bone cell metabolism secondary to carbonic anhydrase inhibition.

Acetazolamide↗
PubMed1986

Vitamin D3 and avian bone in vitro: stimulation of calcium movement into Japanese quail calvaria.

Addition of 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) to cultured neonatal mouse calvaria has consistently led to bone resorption as determined by an increase in medium calcium. No such effect on avian bone has been widely reported. We have tested the in vitro effects of 1,25(OH)2D3 on 48- and 96-hour cultures of calvaria removed from both sexes of Japanese quail at various ages. No effect of 1,25(OH)2D3 on net calcium movement was seen in cultures of calvaria removed from neonatal (5-day), 1-week, and 2-week-old quail. In cultures of calvaria from 6-week-old female quail, addition of 1,25(OH)2D3 resulted in a fall in medium total and ionic calcium concentrations after 48 and 96 hours of incubation, indicating an uptake of calcium by the bones. A maximal effect was seen at 1 X 10(-7) M 1,25(OH)2D3. Bones removed from male and female quail showed no difference in response between the sexes. Bones removed from 5-, 4-, and 3-week-old male and female quail exhibited a progressively decreasing response with decreasing age. After 6 weeks of age female birds begin to exhibit hypercalcemia associated with reproductive activity. Bones removed from 7- and 8-week-old female quail responded to 1,25(OH)2D3 in a similar fashion whether they were hypercalcemic (7 weeks, 20.3 mg/dl; 8 weeks, 31.7 mg/dl), or normocalcemic (10.1 mg/dl). This stimulatory effect of 1,25(OH)2D3 on calcium uptake by avian bone is in sharp contrast to the hormone's effect in cultures of perinatal mammalian bones, which consistently respond to 1,25(OH)2D3 by releasing calcium into the medium.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1986

Forskolin-induced bone resorption in neonatal mouse calvaria in vitro.

The role of cyclic adenosine 3',5'-monophosphate (cAMP) in inducing bone resorption was studied in neonatal mouse calvaria in vitro. Forskolin, a stimulator of adenylate cyclase, increased the medium calcium concentration at 96 hr of incubation, indicating enhanced bone resorption. Bone resorption was observed between 1 X 10(-4) and 1 X 10(-6) M forskolin; the maximal effect was at 1 X 10(-5) M and there was no effect at 1 X 10(-7) M. Lactic acid release was increased during the 96 hr of incubation in proportion to the calcium release in the media. The bone acid phosphatase activity was increased and the alkaline phosphatase activity was decreased. Bone carbonic anhydrase activity was increased more than twofold. Forskolin-induced bone resorption was significantly but incompletely inhibited by 10(-4) M acetazolamide, a carbonic acid anhydrase inhibitor. These findings support the concept that carbonic anhydrase plays a significant role in bone resorption.

Acetazolamide↗
PubMed1986

Bone resorption induced by parathyroid hormone and dibutyryl cyclic AMP: role of carbonic anhydrase.

The role of carbonic anhydrase in bone resorption induced by parathyroid hormone (PTH) and dibutyryl cyclic AMP (DBcAMP) was studied using an in vitro neonatal mouse half-calvarial culture system. Both PTH (16.7 nM) and DBcAMP (0.3 mM) were effective in stimulating bone resorption, as assessed by measuring changes in media calcium concentrations. Bones treated with PTH or DBcAMP for 96 hr contained significantly greater carbonic anhydrase activity than control bones [PTH Treated/Control (T/C) = 2.44; DBcAMP T/C = 2.34]. Both PTH and DBcAMP significantly enhanced calvarial acid phosphatase activity relative to control values [PTH T/C = 1.48; DBcAMP T/C = 1.30]. Neither PTH nor DBcAMP significantly altered calvarial alkaline phosphatase activity. Bone resorption induced by PTH and DBcAMP was inhibited by the carbonic anhydrase inhibitor acetazolamide, but not by the acetazolamide analog CL 13,850 (N-t-butylacetazolamide), which does not inhibit carbonic anhydrase. These results support the concepts that PTH-induced bone resorption requires the action of osteoclastic carbonic anhydrase and that the action of PTH on bone is mediated, in part, by the action of cyclic AMP.

Acetazolamide↗
PubMed1985

Role of carbonic anhydrase in bone resorption induced by 1,25 dihydroxyvitamin D3 in vitro.

The present investigation was undertaken to study the role of carbonic anhydrase in 1,25 dihydroxyvitamin D3-induced bone resorption. Calvaria were removed from 5- to 6-day-old mice and cultured for periods up to 96 h in Dulbecco's Modified Eagle Medium (high glucose, 4,500 mg/dl) supplemented with antibiotics and either heat-inactivated horse and fetal calf sera or bovine serum albumin. The experimental cultures contained 1 X 10(-8) M 1,25 dihydroxyvitamin D3 (1,25(OH)2D3). All cultures were incubated at 37 degrees C in 5% CO2/95% air. Bone resorption was assessed by release of stable calcium into the medium. Bone enzymes (acid and alkaline phosphatases and carbonic anhydrase) were determined following homogenization in 0.25 M sucrose. The effects of 1,25(OH)2D3 were studied in the presence and absence of the carbonic anhydrase inhibitor acetazolamide and its analogue (CL 13,850), which lacks inhibitory activity. Acetazolamide inhibited 1,25(OH)2D3-induced calcium release in a dose-dependent fashion from 10(-5)-10(-4)M. When added to the cultures at a concentration of 1 X 10(-4)M, acetazolamide completely blocked the 1,25(OH)2D3-induced calcium release, a phenomenon not seen with an equimolar concentration of CL 13,850. The most significant finding was that 1,25(OH)2D3-induced calcium release was accompanied by a significant increase in the carbonic anhydrase activity of bone at both 48 (treated/control ratio = 2.05) and 96 (treated/control ratio = 2.59) hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetazolamide↗
PubMed1985

Role of carbonic anhydrase in bone resorption induced by prostaglandin E2 in vitro.

The possible role of carbonic anhydrase in bone resorption induced by prostaglandin E2 (PGE2) was studied using an in vitro neonatal mouse calvarial culture system. PGE2 (10(-6) M) was effective in stimulating resorption, as assessed by calcium release into culture media. This enhanced resorption was accompanied by significant increases in calvarial carbonic anhydrase activity over control values at 48 and 96 h. At 48 h, bones treated with PGE2 had 20% more carbonic anhydrase activity than controls. By 96 h, treated bones contained 79% more carbonic anhydrase activity than controls. PGE2-induced bone resorption was inhibited by the carbonic anhydrase inhibitor acetazolamide in a dose-dependent fashion from 10(-5) to 10(-4) M, with 77% inhibition observed at 10(-4) M. The acetazolamide analogue CL 13,850 (N-t-butylacetazolamide), which does not inhibit carbonic anhydrase, failed to inhibit PGE2-induced resorption. These results are consistent with the hypothesis that carbonic anhydrase is a necessary component of the osteoclastic bone resorptive mechanism.

Animals↗
PubMed1983

Characterization of a high activity carbonic anhydrase isozyme purified from erythrocytes of Salmo gairdneri.

1. A single, high specific activity carbonic anhydrase (CA) isozyme was present in erythrocytes of the teleostean species Salmo gairdneri (rainbow trout). 2. Purification of trout CA to homogeneity was accomplished using chloroform ethanol extraction, Sephadex G-75 gel filtration, and DEAE Bio-Gel anion exchange chromatography. 3. Trout CA was a zinc metalloenzyme of mol. wt 28,300 and pI9.3. 4. Amino acid analysis indicated the presence of 6 half-cystine residues per enzyme molecule, and the presence of a sulfhydryl reducing agent was required to maintain full activity in vitro. 5. Sulfhydryl modification with both N-ethylmaleimide and acrylonitrile indicated the presence of 3 reactive sulfhydryl groups per CA molecule. Modification of those groups had no direct effect on enzyme activity, but modified CA was no longer subject to inactivation by oxidizing conditions.

Acetazolamide↗
PubMed1979

Purification and partial characterization of high and low activity carbonic anhydrase isoenzymes from Malaclemys terrapin centrata.

1. High activity (CA C) and low activity (CA B) carbonic anhydrase isoenzymes have been purified from turtle erythrocytes. 2. The two isoenzymes differed in CO2 hydration specific activity by 36-fold. 3. The low activity isoenzyme contained one half-cystine residue, whereas the high activity isoenzyme contained four half-cystines and required a reducing environment to maintain activity. Both isoenzymes contained zinc. 4. Molecular weights of 28,500 and 30,400 daltons were established for the low and high activity isoenzymes respectively. 5. Both isoenzymes were inhibited by acetazolamide, but only the high activity isoenzyme was inhibited by parachloromercuribenzoate. 6. The low activity isoenzyme was present in the erythrocytes at about 8-10 times the concentration of the high activity isoenzyme. 7. The high activity isoenzyme cross-reacted with antibodies prepared against pure chicken carbonic anhydrase C.

Animals↗