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Biomedical subjects

C M Taylor

Publications and source records attributed to C M Taylor.

At least 163 records · Page 9Linked to original sources
PubMed1984

Estrogen receptor-mediated and cytotoxic effects of the antiestrogens tamoxifen and 4-hydroxytamoxifen.

The triphenylethylene antiestrogen tamoxifen (TAM) is believed to exert its antitumor effect via the estrogen receptor (ER). To test this hypothesis and to differentiate between ER-mediated and general cytotoxic effects of TAM, the growth-inhibitory effects of TAM and its in vivo metabolite 4-hydroxytamoxifen (OH-TAM) have been studied in five continuous human cancer cell lines, MCF7 and T47D (mammary carcinoma, ER positive), BT20 and MDA-MB-231 (mammary carcinoma, ER negative), and ME8 (melanoma, ER negative). All five cell lines are completely killed by concentrations of TAM and OH-TAM above 10(-6) M, regardless of ER status. TAM and OH-TAM have little effect on the ER-negative lines at concentrations below 10(-6) M, whereas the ER-positive lines are highly sensitive to TAM at 10(-7) M and to OH-TAM at 10(-9) M. Inhibition of growth parallels the relative affinity of these drugs for the ER. We conclude that, above 10(-6) M, the growth-inhibitory effects of TAM and OH-TAM in tissue culture are the results of a mechanism other than that via the ER system and that only at lower concentrations are the true ER-mediated effects seen. Plasma concentrations of TAM and OH-TAM in breast cancer patients treated with TAM are in the same range as the concentrations in vivo at which growth inhibition is seen, leading to the conclusion that both compounds contribute to the overall effect of TAM in vivo.

Binding, Competitive↗
PubMed1983

Unilateral nephrectomy and 1,25-dihydroxyvitamin D3.

Several renal functions respond to nephron loss by a compensatory adaptation. Whether the production of 1,25(OH)2D3 also adapts to a renal mass reduction is still a matter of controversy. In the present study we have investigated in rats the influence of unilateral nephrectomy, in both the acute (48 hr) and chronic (2 to 6 weeks) state, on plasma 1,25(OH)2D3 level measured by competitive protein binding assay. In the acute state no difference in plasma 1,25(OH)2D3 level between sham-operated (SHAM) and unilateral-nephrectomized (UNI-NX) rats was found. The presence of the thyroparathyroid glands was not required for maintaining plasma 1,25(OH)2D3 at a normal level 48 hr after UNI-NX. In the chronic state in rats fed at 1.1% Ca diet, plasma 1,25(OH)2D3 (means +/- SEM) was 94 +/- 4 in SHAM and 98 +/- 8 pM in UNI-NX. In rats fed a 0.1% Ca diet it was 252 +/- 16 in SHAM and 239 +/- 20 pM in UNI-NX. Analysis of 3H-1,25(OH)2D3 plasma decay curve indicated that in UNI-NX under a high calcium diet the normalization of plasma 1,25(OH)2D3 appears to be entirely due to an increase in production, whereas under a low calcium diet part of it may also result from a moderate decrease in the elimination rate. In conclusion, this study indicates that unilateral nephrectomy does not affect the level of plasma 1,25(OH)2D3 even under a calcium restriction challenge. This compensatory adaptation appears to be independent of parathyroid hormone.

Animals↗
PubMed1983

An evaluation of multiple trauma severity indices created by different index development strategies.

Evaluation of the effectiveness of emergency trauma care systems is complicated by the need to adjust for the widely variable case mix found in trauma patient populations. Several strategies have been advanced to construct the severity indices that can control for these population differences. This article describes a validity and reliability comparison of trauma severity indices developed under three different approaches: 1) use of a multi-attribute utility (MAU) model; 2) an actuarial approach relying on empirical data bases; and 3) an "ad hoc" approach. Seven criteria were identified to serve as standards of comparison for four different indices. The study's findings indicate that the index developed using the MAU theory approach associates most closely with physician judgments of trauma severity. When correlated with a morbidity outcome measure, the MAU-based index shows higher levels of agreement than the other indices. The index development approach based on the principles of MAU theory has several advantages and it appears to be a powerful tool in the creation of effective severity indices.

Actuarial Analysis↗
PubMed1983

Rapidity of plasma 1,25-dihydroxyvitamin D responses to hypo- and hypercalcemia in steers.

Experiments were designed to study the rapidity of changes in plasma 1,25-dihydroxyvitamin D [1,25-(OH)2D] levels in response to hypercalcemia and hypocalcemia induced by 10-h infusions of CaCl2 or EGTA in steers. In response to CaCl2 infusions, 1,25-(OH)2D was decreased within 4 h (P less than 0.05) and remained lower (P less than 0.05) than preinfusion concentrations for up to 14 h after termination of the infusions. PTH and inorganic phosphate (Pin) transiently decreased in response to the CaCl2 infusions, whereas total magnesium (Mg) continuously fell for up to 24 h after the start of the infusions. In response to infusions with EGTA, on the other hand, 1,25-(OH)2D continuously increased and was raised significantly (P less than 0.05) between 12 and 24 h after the start of the infusions. PTH increased within 2 h (P less than 0.05) and remained elevated (P less than 0.05) for up to 2 h after the end of the EGTA infusions, whereas Pin and Mg were not significantly changed. During and after 10-h control infusions of sodium chloride, the levels of 1,25-(OH)2D, PTH, Ca, Ca++, Pin, and Mg remained unaltered. In conclusion, plasma levels of 1,25-(OH)2D were lowered in response to hypercalcemia within 4 h and increased in response to hypocalcemia within 12 h. After termination of the infusions with CaCl2 or EGTA, levels of 1,25-(OH)2D remained decreased or elevated for at least 14 h, even though Ca, Ca++, and PTH levels were normalized. The slow changes in 1,25-(OH)2D contrast with the rapid responses of PTH to hyper- and hypocalcemia.

Animals↗
PubMed1983

The feasibility of screening preschool children for urinary tract infection using dipslides.

Preschool children were screened for urinary tract infection (UTI) using Oxoid dipslides. A colony count of greater than 10(5) per ml was obtained from 64 out of 566 boys, and 58 out of 446 girls. A diagnosis of UTI was established in 3 boys, all aged 6 months or less, and 5 girls. No child was found to have either vesico-ureteric reflux (VUR) or renal scarring. False positive results were obtained in 15-17% of male and female infants and were attributable to the obligatory use of bag urine collection. These high rates preclude the use of this method in identifying UTI in preschool children on a wide scale.

Child, Preschool↗
PubMed1982

Micturition symptoms and unstable bladder activity in girls with primary vesicoureteric reflux.

A series of 37 girls with primary vesicoureteric reflux of grade II and greater severity underwent urodynamic investigations. Twenty-eight (75%) were found to have unstable bladder activity. Disordered micturition patterns were common and persisted after urinary tract infections had been eradicated. Twenty-six girls had urgency of micturition and 19 urge incontinence occurring once per week or more. The correlation between these symptoms and unstable bladder activity was significant (P less than 0.01), but there was no correlation between bladder instability and the incidence of renal scarring.

Adolescent↗
PubMed1982

Clinical limitations of the estimation of glomerular filtration rate from height/plasma creatinine ratio: a comparison with simultaneous 51Cr edetic acid slope clearance.

A retrospective comparison of single determinations of glomerular filtration rate measured by 51chromium-edetic acid slope clearance (CEDTA) and height/plasma creatinine ratio (Ht/PC) was undertaken in 199 children aged between 3 and 16 years. Analysis of the data indicated that only if Ht/PC less than or equal to 1.2 cm/mumol per 1 was the relationship between Ht/PC and CEDTA linear. Over this range where renal function is significantly impaired the confidence limits for individual prediction of glomerular filtration rate were so wide that a definitive measurement of renal function would be necessary in clinical practice. Where Ht/PC greater than or equal to 1.2 the relationship was non-linear and the predictive confidence limits very wide. To apply the technique as a screening test for normal renal function (CEDTA greater than or equal to 80 ml/min per 1.73 m2) the Ht/PC would need to exceed 2.16. In our study this would have detected 57 out of 131 patients who had normal glomerular filtration rates and erroneously included 2 out of 68 with subnormal renal function.

Adolescent↗
PubMed1982

The biosynthesis of glycoproteins by cultured bovine tendon fibroblasts.

Confluent bovine fetal tendon fibroblasts maintained in a chemically defined medium incorporated L-[6-3H]fucose and L-[5-3H]proline in a linear manner into non-diffusible macromolecules for up to 48 hrs. Equilibrium CsCl density gradient centrifugation indicated that [3H]fucose-labelled macromolecules released into the medium were predominantly glycoproteins. The [3H]fucose-labelled glycoproteins in the culture medium were analyzed by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. This technique demonstrated the presence of a number of high mol. wt. fucosylated components, the most notable of which was a glycoprotein of apparent mol. wt. 150,000. Immunological procedures allowed the tentative identification of four glycoproteins including fibronectin which was found in the cell medium and in extracts of the cell layer. Two of the glycoproteins (mol. wts. 150,000 and 270,000) released into the incubation medium were shown to be related to the microfibrillar components of elastic tissue. One or more of the newly synthesized [3H]fucose labelled molecules was shown to be immunologically related to a glycoprotein (mol. wt. 60,000) extracted from bovine Achilles tendon. These studies represent the first demonstration of the synthesis of microfibril-related and tendon glycoprotein-related macromolecules by tendon fibroblasts in culture.

Achilles Tendon↗
PubMed1982

Effect of vitamin D2 on the assay of 24,25-dihydroxyvitamin D3 in man.

Serum levels of the dihydroxylated metabolite of vitamin D3, 24,25-dihydroxycholecalciferol (24, 25(OH)2D3) were measured by competitive protein-binding assay in 2 anephric patients while undergoing therapy with 25-hydroxycholecalciferol (25(OH)D3) and, at a later date, vitamin D2, ergocalciferol. Whereas there was no increase in serum levels of 24, 25 (OH)2D3 when the patients were treated with 25 (OH)D3, a significant increase was apparently seen when vitamin D2 was given. These results suggest that a metabolite of vitamin D2, non-renal in origin, may be interfering in the assay for 24, 25 (OH)2D3. The different levels of serum 24, 25 (OH)2D3 in anephric man found by various groups of workers are explained by these results.

24,25-Dihydroxyvitamin D 3↗
PubMed1981

Effects of 24,25-dihydroxy-vitamin D3 on its plasma level in man.

Small doses of 24,25-dihydroxy-vitamin D3 (24,25(OH)2D3; 2 micrograms daily) given by mouth increased plasma levels of 24,25(OH)2D3 several-fold in normal subjects and in patients with metabolic bone disease. When oral treatment was stopped, or following the intravenous administration of 24,25(OH)2D3, plasma disappearance of 24,25(OH)2D3 was slow (t1/2 approx. 16 days). This suggests that the endogenous production rate of 24,25(OH)2D3 is similar to that of 1,25(OH)2D3 (less than 2 micrograms daily) but that its metabolic clearance is much slower. The slow metabolic clearance of 24,25(OH)2D3 may explain why plasma levels of this metabolite are about 100 times higher than those of 1,25(OH)2D3.

24,25-Dihydroxyvitamin D 3↗
PubMed1981

Plasma levels of vitamin D metabolites in diphosphonate-treated rats.

1. Protein-binding assays have been used to measure plasma 1,25-dihydroxy-vitamin D [1,25-(OH)2D] as well as 25-hydroxy-vitamin D [25-(OH)D] in rats given 10 mg of phosphorus (P) day(-1) kg(-1) as ethane-1-hydroxy-1,1-diphosphonate (EHDP). 2. In control animals given a normal laboratory chow plasma 25-(OH)D and 1,25-(OH)2D were about 40 nmol/l and 300 pmol/l respectively. 3. EHDP produced a decrease of plasma 1,25-(OH)2D to below 50 pmol/l in 2 days. 4. Both in control and in EHDP-treated rats plasma 1,25-(OH)2D increased when dietary calcium (Ca) was restricted to 0.1%, or dietary P to 0.2%, indicating that the well-known stimulatory effect of Ca or P deprivation was at least partially effective in EHDP-treated rats. 5. In response to an increase of the oral supply of vitamin D3 to 65 nmol/day the plasma level of 25-(OH)D rose in both control and EHDP groups. Plasma 1,25-(OH)2D was not increased above the normal value in control rats. In EHDP-treated rats, however, plasma 1,25-(OH)2D rose to a level equal to that in controls, suggesting that the effect of EHDP on plasma 1,25-(OH)2D can be overcome at high precursor concentration.

25-Hydroxyvitamin D 2↗