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Biomedical subjects

D Richardson

Publications and source records attributed to D Richardson.

At least 19 recordsLinked to original sources
PubMed1992

Two mechanisms of iron uptake from transferrin by melanoma cells. The effect of desferrioxamine and ferric ammonium citrate.

The effects of ferric ammonium citrate (FAC) and desferrioxamine (DFO) on iron (Fe), and transferrin (Tf) uptake have been investigated using SK-MEL-28 human melanoma cells, which express the Tf homologue, melanotransferrin, in high concentrations. Previously we demonstrated two separate Fe uptake mechanisms from Tf, viz. a specific process mediated by the transferrin receptor (TfR) and a nonspecific process (Richardson, D. R., and Baker, E. (1990) Biochim. Biophys. Acta 1053, 1-12). Cells exposed to DFO demonstrated up-regulation of the TfR with a concurrent increase in the rate of Fe uptake. Desferrioxamine also stimulated the nonspecific process of Fe uptake, resulting in a further increase in accumulation of Fe over Tf after saturation of the specific TfR. Ferric ammonium citrate had two effects. First, it resulted in down-regulation of the TfR. Second, and paradoxically, it markedly stimulated the rate of Fe uptake from Tf by the nonspecific process without increasing the rate of nonspecific Tf uptake. These data conclusively demonstrate that two entirely different mechanisms of iron uptake from Tf exist in melanoma cells and that ferric ammonium citrate may be a useful experimental tool to further characterize the specific and nonspecific mechanisms of Fe uptake from Tf.

Biological Transport↗
PubMed1992

Evaluation of the iron chelation potential of hydrazones of pyridoxal, salicylaldehyde and 2-hydroxy-1-naphthylaldehyde using the hepatocyte in culture.

A range of new analogues of the promising iron chelator pyridoxal isonicotinoyl hydrazone was prepared and assessed for activity in reducing hepatocyte iron, mechanism of action and potential in iron-chelation therapy. A total of 45 compounds were synthesized by condensation of aromatic aldehydes (pyridoxal, salicylaldehyde and 2-hydroxy-1-naphthylaldehyde) with various acid hydrazides prepared by systematic substitutions on the benzene ring or by the replacement of the ring with an acetyl, pyridyl, furoyl or thiophene moiety. The effects of these compounds on 59Fe uptake and intracellular distribution in hepatocytes in culture and on 59Fe mobilization from prelabeled hepatocytes were assessed. Toxicity, lipophilicity and the ability to chelate plasma transferrin-bound 59Fe were also evaluated. Several compounds were much more active than pyridoxal isonicotinoyl hydrazone and may have clinical potential. These included pyridoxal benzoyl hydrazone, pyridoxal p-methoxybenzoyl hydrazone, pyridoxal m-fluorobenzoyl hydrazone and pyridoxal 2-pyridyl hydrazone. All were more effective at reducing iron uptake than mobilizing hepatocyte iron; they also may act primarily on the transit iron pool rather than on storage iron. Other compounds (e.g., salicylaldehyde p-t-butyl-benzoyl hydrazone) redistributed ferritin-59Fe to different intracellular sites but had little net effect on hepatocyte iron levels.

Animals↗
PubMed1992

In vivo MR evaluation of Gd-DTPA conjugated to dextran in normal rabbits.

A dextran-Gd-DTPA compound has been recently synthesized utilizing 70,800 Da molecular weight dextran. This polymeric contrast agent for magnetic resonance imaging has been found chemically to be very stable and to demonstrate in vitro improved relaxivities of 1.5 to 2.3 times that of monomeric Gd-DTPA at 100 MHz. This MR experiment examines the in vivo distribution and relaxivity of the 70,800 Da molecular weight dextran-Gd-DTPA compound in a rabbit model by measuring the change in signal-to-noise ratio of a variety of organs (renal cortex, renal medulla, liver, brain, and torcula herophile) compared to the preinjection state. Results demonstrate prolonged (beyond 60 min) enhancement of the renal cortex, renal medulla, liver and torcula, and no enhancement of brain parenchyma.

Animals↗
PubMed1992

Attenuation of the cutaneous vasoconstrictor response to cold in elderly men.

This study tested the hypothesis that the cutaneous vasoconstrictor response to cold is reduced in elderly individuals. We measured laser Doppler flux (LDF) in the fingertip and blood cell velocity (CBV), via videodensitometry, in individual capillaries of the finger nailfold both before and during submersion of the contralateral arm in a 15 degrees C water bath. Subjects were 10 young (M = 25 years) and 10 old (M = 71 years) male adults. During the first minute of cooling, both the young (Y) and old (O) groups experienced a significant (p < .004) decrease in LDF. Over the subsequent 4 minutes of cold stress, LDF remained significantly depressed in the Y group, whereas LDF returned to values not significantly different from pre-cooling control in the O subjects. During the cold stress, CBV significantly decreased in the Y (p < .03) subjects; however, the degree of change was much less than that of LDF (49% decrease in LDF versus 14% decrease for CBV). In contrast to the Y subjects, the O group showed no significant change in CBV during cooling (p > .28). These results indicate that indirect cooling elicits a reflex decrease in cutaneous bloodflow, which is more pronounced in the deep vessels than in the superficial capillaries, and that these effects are attenuated with advancing age.

Adult↗
PubMed1992

On the pharmacological and physiological role of glibenclamide-sensitive potassium channels in colonic smooth muscle.

Actions of activators of glibenclamide sensitive K+ channels on canine colonic circular muscle were investigated. Cromakalim as well as its (-) enantiomer lemakalim caused inhibition of spontaneous phasic contractile activity (EC50's 4.4 +/- 0.1 x 10(-7) M and 2.3 +/- 0.4 x 10(-7) M, respectively) and of carbachol induced activity (EC50's: 9.4 +/- 5.1 x 10(-7) M and 4.3 +/- 1.4 x 10(-7) M, respectively). Cromakalim and lemakalim effects were completely inhibited by glibenclamide. Additive effects between K+ channel activators and other drugs relaxing colonic muscle (the L-type calcium channel blocker D600 and forskolin) were seen. A physiological role for specific glibenclamide sensitive K+ channels, if existing, remains unresolved. The present study indicates that the non-adrenergic inhibitory nerves do not act through these channels, neither does stimulation of muscarinic or beta-adrenergic receptors.

Animals↗
PubMed1992

Effects of kwashiorkor malnutrition on measured capillary filtration rate in forearm.

This study investigated the effects of kwashiorkor malnutrition on blood tissue fluid exchange by measuring the rate of capillary filtration (CFR) in response to a 60-mmHg increment in venous pressure in the forearms of 1- to 3-yr-old native African children within the Transkei Homeland. They were divided into the following subject groups: kwashiorkor patients (K); kwashiorkor patients who were at various stages of recovery (RK); marasmus patients (M); patients with edema of nonkwashiorkor origin (E); and control children (C). Measurements of CFR were significantly lower in the K subjects compared with any of the other groups (P less than 0.05), whereas, the RK, M, E, and C subjects were not significantly different from each other. This latter finding indicates that the lower CFR of the K patients is reversible and is not due to malnutrition or edema per se. Measurements of forearm cutaneous blood flow by laser Doppler flowmetry (LDF) in C and K subjects showed only a slightly lower value for the K patients (P greater than 0.20), and there was no relationship between CFR and LDF for either group (r = 0.073). These results suggest that the lower CFR of the K patients is not secondary to peripheral vasoconstriction.

Anthropometry↗
PubMed1992

Blunt cardiac injury.

Explore the source record for details and available documents.

Abbreviated Injury Scale↗
PubMed1992

Women, AIDS and reproduction.

Relatively little has been written about how Aids affects women. When women are mentioned it is primarily as carers of people with Aids or as possible transmitters of the HIV virus, with the focus largely on prostitutes and pregnant women. The concern overwhelmingly is about how to protect the health of men and children, writes Diane Richardson. Here she examines the implications of Aids and HIV infection for women's health and reproductive rights.

Acquired Immunodeficiency Syndrome↗
PubMed1991

The uptake of inorganic iron complexes by human melanoma cells.

The human melanoma cell line, SK-MEL-28, expresses high levels of melanotransferrin. The uptake of inorganic iron (Fe) complexes compared to transferrin-bound Fe by these cells has been investigated to determine whether melanotransferrin has a role in Fe uptake. The mechanisms of Fe uptake have been characterised using 59Fe complexes of citrate, nitrilotriacetate, desferrioxamine, and 59Fe added to Eagle's minimum essential medium (MEM) and compared with human transferrin (Tf) labelled with 59Fe and iodine-125. Iron uptake from the Fe complexes of citrate, nitrilotriacetate and MEM were similar, and far greater than that from Tf at the same Fe concentration (2.5 microM). Ammonium chloride and a monoclonal antibody to the transferrin receptor (42/6), had no effect on the uptake of Fe from inorganic Fe complexes, suggesting that receptor-mediated endocytosis of Tf was not involved. The monoclonal antibody, 96.5, specific for melanotransferrin did not alter total Fe uptake but slightly increased the proportion of Fe internalised, possibly due to the modulation of the antigen by the antibody. However, from the time required for modulation to occur (approximately 2 h), the small increase in internalisation observed and the fact that no increase in total cell Fe occurred, it is suggested that melanotransferrin has little role in Fe uptake.

Ammonium Chloride↗
PubMed1991

Repair of shoulder luxation in a horse.

Shoulder luxation in a 3-year-old Thoroughbred filly was treated by closed reduction, using a calf jack to provide traction on the limb. Arthroscopic examination of the shoulder allowed removal of soft tissue and bony debris. After surgery, the filly was confined to a box stall for 6 months. Eight months after surgery, the filly was doing light work and was not lame. Muscular atrophy present before surgery had resolved. Use of a calf jack may allow reduction of shoulder luxation under field conditions.

Animals↗
PubMed1991

The cutaneous microcirculation of the forearm in young and old subjects.

Previous studies have shown a reduced cutaneous circulatory response to direct heat stress in the forearm circulations of older (60 to 80 year) subjects. The purpose of this study was to test the hypothesis that this aging effect is due to a reduced ability of the cutaneous microvessels in the forearm to respond to direct heat. Two groups of male subjects consented to participate; a group of 15 young individuals (Y; 20-39 year) and a group of 11 older (O; 60-79 year) individuals. The subjects rested in a supine position with the right forearm situated on the stage of a Leitz epiilumination microscope which was used to view the superficial cutaneous microvessels. The width of the red cell column (WRC), an index of vascular diameter, and the blood cell velocity (BCV) within the microvessels were measured by videomicroscopy at the presenting skin temperature (Ts) of 32 degrees, and then again after Ts had been elevated to 35 degrees then 40 degrees. At a Ts of 32 degrees, WRC and BCV for the Y group, respectively, averaged 6.6 microns and 0.22 mm/sec. Corresponding averages for the O subjects were 8.4 microns and 0.17 mm/sec. Between-group differences were not significant. At a skin temperature of 40 degrees, BCV was significantly higher compared to that at 32 degrees and 35 degrees for both groups (P less than 0.05); whereas, WRC did not significantly change. There were no significant between-group differences in BCV at the higher two temperatures. These results argue against a diminished blood flow response of superficial microvessels being responsible for the reduced cutaneous circulatory response to heat stress in older individuals.

Adult↗
PubMed1991

Anterior maxillary osteoplasty to broaden the narrow maxillary ridge.

The application of endosseous implants has extended the range of options and effectiveness of reconstructive preprosthetic surgery. Placement of endosseous implants in the edentulous maxilla is often restricted due to lack of available bone. Exposure of the underlying anterior maxillary bone frequently reveals a ridge form which is adequate in height but too narrow to accommodate endosseous implants. A horseshoe type osteotomy extending from the ridge crest into the floor of nose has been developed which allows advancement of the outer cortex to restore lost facial form and placement of an interpositional bone graft and endosseous implants to restore lost function.

Adolescent↗
PubMed1991

Effects of invariant sympathetic activity on cutaneous circulatory responses to heat stress.

This study investigated the role of sympathetic withdrawal on blood flow responses in cutaneous arteriovenous anastomoses (AVAs) and capillaries to direct and indirect heat stress. This was achieved by clamping sympathetic activity (SC) to the tail of anesthetized rats so that constrictor tone remained invariant during exposure of either the animal's tail (direct heating) or body (indirect heating) to a 35 degrees C environment. Flow through the AVAs in the tail was evaluated by laser-Doppler flowmetry (LDF), while capillary flow was investigated by videodensitometry measurements of blood cell velocity (CBV) in single capillaries within the subepidermal vascular plexus. Both direct and indirect heating significantly increased LDF and CBV. In comparison to blood flow responses in sham-operated control rats, the SC procedure resulted in significantly lower LDF responses to both direct and indirect heat stress. By contrast, the response of CBV was not significantly affected by SC during either mode of heating. These results indicate that the withdrawal of sympathetic constrictor tone plays a role in the response of cutaneous AVAs, but not precapillary arterioles, to direct as well as indirect heat stress. Additional studies on unanesthetized animals showed that superimposing body heating on a base of local heating elicited a further increase in LDF, suggesting that local heating does not deplete neural mediated dilatory reserve.

Animals↗
PubMed1991

Studies on yeast nucleoside triphosphate-nucleoside diphosphate transphosphorylase (nucleoside diphosphokinase). IV. Steady-state kinetic properties with thymidine nucleotides (including 3'-azido-3'-deoxythymidine analogues).

A study of the steady-state kinetics of the crystalline brewer's yeast (Saccharomyces carlsbergensis) nucleoside diphosphokinase, with the magnesium complexes of the adenine and thymidine nucleotides as reactants, has led to a postulated kinetic mechanism which proceeds through a substituted enzyme. This agrees with the earlier conclusions of Garces and Cleland [Biochemistry 1969; 8:633-640] who characterized a reaction between the magnesium complexes of the adenine and uridine nucleotides. An advantage of using thymidine nucleotides as reactants is that they permit accurate, rapid and continuous assays of the enzymatic activity in coupled-enzymatic tests. Through measurements of the initial velocities and product inhibition studies, the Michaelis constants, maximum velocities, and inhibition constants could be evaluated for the individual substrates. Competitive substrate inhibition was encountered at relatively high substrate concentrations, which also permitted an evaluation of their ability to act as 'dead-end' inhibitors. The Michaelis constants for the 3'-azido-3'-deoxythymidine (AzT) analogues were also evaluated and, although these values were only somewhat higher than those of their natural substrates, the Km's for the adenine nucleotides as paired substrates were lower and the Vmax's were drastically reduced. The pharmacological implications of these observations are touched upon and extrapolated to the cases where therapeutic doses of AzT may be employed.

Adenine Nucleotides↗