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Biomedical subjects

K F Kelly

Publications and source records attributed to K F Kelly.

28 records · Page 2Linked to original sources
PubMed1989

In vitro antiproliferative activity of 4-substituted 2-(2-hydroxyphenyl)thiazolines on murine leukemia cells.

Two previously synthesized and two structurally novel thiazoline iron chelators are described. N4-Benzyl-N1,N8-bis[[2-(2-hydroxyphenyl)thiazolin-4-yl]carbonyl] homospermidine (5) proved to be the most potent antiproliferative and cytocidal compound in the series with in vitro IC50 values of 3 and 1 microM on L1210 and P388 murine cell lines. The N4-acetyl analogue 7 was considerably less active than 5 with IC50 and cell viability values that were similar to those of the structurally simple thiazolines 2 and 3. The antiproliferative activity of 3 and 7 could be substantially reduced or ablated by delivery to cell suspensions as a 1:1 molar mixture with FeCl3, while the activity of 5 was unaffected by Fe(III) chelation. As expected, 3 induced a G1/S cell cycle block at the 100 microM block consistent with interference with DNA synthesis while 10 microM 5 did not affect L1210 cell cycle distribution. Tritiated thymidine incorporation studies confirmed that 5 was incapable of interfering with DNA synthesis at concentrations below 40 microM. Alkaline elution studies indicate that 5 does not cause DNA strand breaks in vitro at concentrations of 10 microM. The N4-benzyl group of 5 appears to impart in vitro potency as the N4-acetyl analogue 7 lacks comparable in vitro antiproliferative and cytocidal activity.

Animals↗
PubMed1989

Linkage in a family with X-linked Charcot-Marie-Tooth disease.

The gene for the X-linked form of Charcot-Marie-Tooth disease (CMT Peroneal Muscular Atrophy, X-linked: McKusick No. 30280) has been shown in a single family to be linked to DXYS1 with a lod score of 4.55 at a recombination fraction of 0.03 and to PGK1 with a lod score of 3.34 at zero recombination. This is in agreement with previous work based on several families. Pooled data from this family and 7 previously reported families give a maximum lod score of 12.04 at theta max of 0.05 for linkage between CMTX and DXYS1 loci.

Charcot-Marie-Tooth Disease↗
PubMed1988

In vitro antiproliferative activity of 2'-(2-hydroxyphenyl)-2'-thiazoline-4'-carboxylic acid and its methyl ester on L1210 and P388 murine neoplasms.

The activity of three iron chelators, methyl [2'-(2-hydroxyphenyl)-2'-thiazoline-4'-carboxylate] (MTL); 2'-(2-hydroxyphenyl)-2'-thiazoline-4'-carboxylic acid (TFAL); and 2-hydroxyphenyl-imido-ethyl-ether (Imidate), regarding antiproliferative, cytocidal, and cell-cycle effects are reported and compared with hydroxyurea (HU). In vitro, against L1210 and P388 murine neoplasms, MTL and TFAL displayed substantially greater antiproliferative activity than HU, although Imidate displayed no appreciable activity. MTL also induced a statistically more complete G1/S cell-boundary block than did HU at equimolar concentrations (100 microM). The IC50 values produced by MTL and TFAL were low enough (less than or equal to 20 microM) to warrant further testing of these chelators as potential antineoplastic agents.

Animals↗
PubMed1988

Effects of oestrogen on the expression of a 4.4 kb mRNA in the ZR-75-1 human breast cancer cell line.

A cDNA library has been constructed from the poly(A)+ mRNA of oestrogen-stimulated ZR-75-1 human breast cancer cells. Screening by differential hybridization has identified eight clones which are stimulated between 4- and 16-fold by oestrogen. Two clones (pLIV-1) that are stimulated 4-fold, hybridize to three different mRNA species. A further five recombinants encode for a mRNA 600 bp long which is induced greater than 16-fold and have been shown to cross-hybridize to the oestrogen-responsive clone, pS2, isolated from the MCF-7 breast cancer cell line. Oestradiol was shown to be without detectable effect upon the expression of mRNA for dihydrofolate reductase, which is reported to be oestrogen regulated in MCF-7 cells. Actin gene expression is also unresponsive to oestradiol in ZR-75-1 cells. These results suggest that pLIV-1 represents a previously unidentified mRNA that may be involved in the oestrogen-regulated growth of ZR-75-1 human breast cancer cells.

Breast Neoplasms↗
PubMed1983

The transport of orthovanadate and similar oxyanions in relation to salt and water transport across the isolated intestine of the common eel, Anguilla anguilla.

An intestinal preparation from the common eel (Anguilla anguilla) was characterized for both mucosal to serosal and serosal to mucosal transport of water, alanine, sodium and chloride. The preparation showed a net outflux of water and a net influx of alanine, and no net fluxes of sodium or chloride. The influxes of all four substances and the outflux of water were inhibited by ouabain, while the outfluxes of alanine, sodium and chloride were increased by ouabain. Influxes and outfluxes of the oxyanions orthovanadate, phosphate, arsenate, sulphate, selenate and chromate were measured over a range of concentrations from 10(-8) M to 10(-4) M. The entry of each anion was dependent on the mucosal concentration, not saturable within the concentration range used or competitive with chloride. There were no net fluxes of these anions and pertechnecate from solutions containing equal mucosal and serosal concentrations of the anion.

Alanine↗
PubMed1981

Effects of orthovanadate on salt and water effluxes from the gills of seawater eels, Anguilla anguilla.

Orthovanadate (5 . 10(-7) M) perfused through isolated gills at a constant rate increased the perfusion pressure by 40% but inhibited the effluxes of Na+ and Cl- by 40%. Water efflux was unaltered. Ouabain (10(-4) M) and rotenone (10(-4) M) influenced salt and water effluxes in the same way but did not alter perfusion pressures. Orthovanadate (10(-5) M) perfused at constant rate increased the pressure nearly 2.5-fold; under these conditions effluxes of Na+, Cl- and H2O were all increased approximately 2.5-fold.

Anguilla↗
PubMed1981

The uptake from fresh water and subsequent clearance of a vanadium burden by the common eel (Anguilla anguilla).

The uptake of 48V vanadium from a solution of 10(-5) M 48V-orthovanadate by fresh-water elvers and the subsequent depletion of the vanadium burden was studied. At the end of the 8-week loading period, the levels of 48V were still increasing in the liver, kidney, bone and carcase. The uptake rate for the whole fish over the 8-week period was 760 pg atom/h/100 g body wt and the depletion rate over the following 5 weeks in clean water was about one tenth of this. Liver contained the highest amount of 48V at the end of the 8-week loading period, calculated as equivalent to 1.1 x 10(-4) g atom V/kg wet wt, and this level was unchanged at the end of the 5-week depletion period. Less than 1% of the carcase 48V was present in the fraction of MW under 2000.

Anguilla↗
PubMedDate not supplied

No excess of factor V:Q506 genotype but high prevalence of anticardiolipin antibodies without antiendothelial cell antibodies in retinal vein occlusion in young patients.

Factor V:Q506 (factor V Leiden) is associated with venous thrombosis and has been reported to be a risk factor for retinal vein occlusion (RVO). Anticardiolipin antibodies (ACA), also associated with RVO, are a marker for the prothrombotic condition antiphospholipid syndrome, in which antiendothelial antibodies (AECA) are also frequently present. This study reviewed 45 younger patients 10 GPL units); in 6 of these, the titre was >20 GPL units (population reference range = 0-10 GPL units). No patient had antiendothelial cell reactivity. The low-titre ACA may therefore represent a non-specific response to vascular injury.

Activated Protein C Resistance↗