PubMed Health⌕ Search

Biomedical subjects

C D Jones

Publications and source records attributed to C D Jones.

143 records · Page 8Linked to original sources
PubMed1983

Mucociliary clearance from the calf lung.

Mucociliary clearance rate constants for ten calves were obtained using Technetium 99m-sulphur colloid complex. The mean rate constant measured at the lung for all calves was 0.012 (+/- 0.009) min-1 (half-life 58 minutes). The clearance rate constants obtained from measurements made at the larynx were higher (0.02 +/- 0.007 min-1), although not significantly higher, than those determined from measurements taken at the lung. The constants can be used to predict the particle burden on the lungs of calves kept under husbandry systems of varying air hygiene.

Aerosols↗
PubMed1981

Differential interaction of antiestrogens with cytosol estrogen receptors.

Interaction of tamoxifen, trioxifene and LY117018 with cytosol-estrogen receptors from immature rat uteri was compared. Determination of relative binding affinity (RBA) by competition with [3H] estradiol under various assay conditions revealed that the RBA of LY117018 increased with temperature while that of trioxifene declined. Furthermore, the RBA values of tamoxifen and trioxifene observed after 24 h of incubation at 4 degrees C were significantly lower than those obtained with 1-h incubations. However RBA values obtained with 1- or 24-h incubations of LY117018 at 4 degrees C were similar. The complex formed by estradiol or LY117018 at 4 degrees was relatively stable for 24 h, while significant dissociation of tamoxifen and trioxifene was detected under these conditions. At 30 degrees C estradiol displayed a biphasic pattern of dissociation, but tamoxifen and trioxifene dissociated rapidly and little evidence of a stable phase was apparent. By contrast, the complex formed by LY117018 exhibited greater stability than that of estradiol at 30 degrees C. These results establish a relationship between shifts in competition curves (RBA) and rates of dissociation relative to estradiol; and clearly reveal that LY117018 has different binding characteristics than tamoxifen and trioxifene.

Animals↗
PubMed1979

Synthesis and antiestrogenic activity of [3,4-dihydro-2-(4-methoxyphenyl)-1-naphthalenyl][4-[2-(1-pyrrolidinyl)ethoxy]-phenyl]methanone, methanesulfonic acid salt.

Acylation of the sodio anion of beta-tetralone with phenyl anisoate, followed by a Grignard reaction of the resultant 4 with 4-methoxyphenylmagnesium bromide, gave rise to two novel dihydronaphthalene isomers 5 and 6. Regioselective demethylation of either 5 or 6 by NaSEt produced [3,4-dihydro-2-(4-methoxyphenyl)-1-naphthalenyl](4-hydroxyphenyl)methanone (7). Etherification of the phenolic group of 7 by N-(2-chloroethyl)pyrrolidine and subsequent methanesulfonate salt formation provided [3,4-dihydro-2-(4-methoxyphenyl)-1-maphthalenyl]]4-]2-(1-pyrrolidinyl)ethoxy]phenyl]methanone, methane sulfonic acid salt (3). Potent antiestrogenic activity of 3 was demonstrated by both oral and subcutaneous administration to rats and mice. In vitro binding studies with rat uterine cytosol estrogen receptors indicate compound 3 has a very high binding affinity which exceeds that of estradiol.

Animals↗
PubMed1975

The use of 6alpha-and 6beta-carboxymethyl testosterone-bovine serum albumin conjugates in radioimmunoassay for testosterone.

The synthesis of 6alpha- and 6beta-testosterone-bovine serum albumin (BSA) conjugates is described. 6beta-Carboxymethyl-4-androstene-3,17-dione was prepared by a route analogous to that described earlier for 6beta-carboxymethyl progesterone. Sodium borohydride reduction of the 3 and 17 keto groups and subsequent selective oxidation of the resulting 3beta, 17beta-diol using MnO2 provided 6 -carboxymethyl testosterone. Further acid catalyzed epimerization of the C-6 center gave the isomeric 6alpha-carboxymethyl testosterone. The 6alpha- and 6beta-testosterone derivatives were attached to BSA via a mixed anhydride coupling employing tributylamine and i minus-butylchlorocarbonate. For each molecule of BSA, the 6alpha- and 6beta-conjugates contained an average of 23 and 20 steroid residues, respectively. Antisera to the conjugates exhibited similar high specificities toward various steroids, the only incidence of serious cross-reaction being the expected case of dihydrotestosterone.

Androstenedione↗
PubMedDate not supplied

Designing population pharmacokinetic studies: performance of mixed designs.

The interplay of the following factors: population design (PDN), the cost function in terms of maximum cost (Max. C) (i.e., maximum number of samples/sample size), sample size, and intersubject variability [restricted (30%) to moderate (60%)] on the estimation of pharmacokinetic parameters from population pharmacokinetic data sets obtained using mixed designs was investigated in a simulation study. A two compartment model with multiple bolus intravenous inputs was assumed, and the residual variability was set at 15%. The sample size (N) investigated ranged from 30 to 200 with the associated cost function varying accordingly with the five individual and sixteen population designs studied. Accurate and precise estimates of structural model parameters were obtained for N > or = 50 (Max. C > or = 150) irrespective of the intersubject variability (ITV) and PDN investigated. When ITV was 30%, all structural model parameters were well estimated irrespective of the PDN. Robust estimates of clearance and its variability were obtained for all N at all levels of ITV with Max. C > or = 90 (PDN > or = 4). Imprecise estimates of ITV in V1, V2, and Q were obtained at 60% ITV irrespective of N, PDN, or Max. C. Positive bias was associated with the estimation of variability in V1, V2, and Q with PDN < or = 4 (Max. C < or = 150). This was due in part to a greater proportion of subjects sampled only once. Correspondingly, residual variability was underestimated. It is of utmost importance to avoid this artifact by ensuring that at least a moderate subset of subjects contributing data to a population pharmacokinetic study contribute data more than once. Given a sample size and ITV, the cost function must be considered in designing a population pharmacokinetic study using mixed designs.

Humans↗
PubMedDate not supplied

Computed tomographic evaluation and guided correction of malpositioned nephrostomy catheters.

BACKGROUND: To determine the utility of computed tomography (CT) in the detection and correction of malpositioned nephrostomy catheters after contrast spillage during nephrostograms. METHODS: CT was performed in nine patients after an abnormal (contrast spillage) tube nephrostogram performed during or after nephrostomy tube placement. CT was used to locate the nephrostomy catheter position in relation to the renal collecting system. If possible, CT was also used for guidance and repositioning of the nephrostomy catheters into the intrarenal collecting system. RESULTS: In all nine cases, CT was successful in detecting the position of the suspected malpositioned catheter. In seven of nine cases, CT demonstrated the catheter outside the renal collecting system and effectively helped reposition the catheters into the intrarenal collecting system. In one case, the malpositioned nephrostomy catheter was within the intraperitoneal cavity and required surgical correction. Another case required fluoroscopic-guided repositioning for the initial nephrostomy catheter, which was partly posterior to the kidney and partly within the kidney. The catheter in this latter case was successfully advanced over a guidewire into the collecting system. CONCLUSIONS: CT may be used to detect possible catheter malposition associated with nephrostomy tube placement. CT may also be used to successfully guide catheter repositioning in the renal collecting system.

Adult↗
PubMedDate not supplied

Discovery and development of a novel class of nonsteroidal aromatase inhibitors.

Efforts to develop a novel class of nonsteroidal aromatase inhibitors began with the discovery that the infertility in male rats exposed to high levels of the agricultural fungicide, fenarimol (alpha-(2-chlorophenyl)-alpha-(4-chlorophenyl)-5-pyrimidine-methanol), was attributable to the inhibition of aromatase activity within the central nervous system during the critical neonatal period. Although fenarimol was not particularly potent in inhibiting rat ovarian microsome aromatase activity in vitro (50% inhibition (IC50) = 4.1 microM). Subsequent testing of a number of analogues led to the identification of LY56110 (alpha,alpha-bis(4-chlorophenyl)-5-methylpyrimidine) which exhibited an IC50 of 29 nM. LY56110 was orally active, blocking the testosterone-induced increase of uterine weight and ovarian estrogen biosynthesis in immature female rats. In rats with established DMBA-induced mammary carcinoma, complete tumor regression was observed in 80% of the animals. Development of LY56110 was, however, stopped because of its effects on hepatic microsomal enzymes and an unacceptably long half-life. Structural modifications resulted in the development of the indenopyrimidines. LY113174 (8-chloro-5-(4-chlorophenyl)-5H-indeno less than 1, 2D greater than pyrimidine) was highly effective in vitro (IC50 = 24 nM) and in vivo but was far less potent than LY56110 with respect to induction of hepatic microsomal enzymes. LY113174 exhibited an acceptable biological half-life and had no effect on cholesterol side-chain cleavage. The indenopyrimidines appear to be a novel class of nonsteroidal aromatase inhibitors which may prove useful in the treatment of estrogen-dependent diseases.

Animals↗
PubMedDate not supplied

Extension of the Castle-Wright effective factor estimator to sex linkage and haplodiploidy.

The Castle-Wright effective factor estimator gives a minimum estimate of the number of genes underlying complex traits. Because the Castle-Wright estimator does not rely on genetic markers, it is especially useful in genetically undeveloped species. In this article I describe two extensions of this estimator. The first corrects the estimator in heterogametic (XY) species with a partially sex-linked trait. In this case the traditional estimator underestimates gene number in F2 males and overestimates it in F2 females and backcross females and males. The second extension adapts the Castle-Wright equation to haplodiploid species.

Algorithms↗
PubMedDate not supplied

A polymorphism in the BCL-6 gene is associated with follicle center lymphoma.

Follicle center lymphoma (FCL) accounts for approximately 40% of all non-Hodgkin's lymphomas (NHL). The genetic-environmental interactions involved in the etiology and pathogenesis of this disease are unknown. In our previous study a single nucleotide polymorphism (SNP) (397C) in the regulatory untranslated first intron region of the BCL-6 gene was found in four of the eight FCL patients but in none of the 10 healthy controls. To further evaluate the potential association between the 397C allele of the BCL-6 gene and FCL, we performed a case-control study. Genomic DNA was isolated from 85 FCL patients, from 98 control cases without a previous history of malignancy, treated at Stanford University Medical Center for non-malignant disorders and from 90 samples from the DNA Polymorphism Discovery Resource. The 397G and the 397C polymorphic alleles were identified by a PCR-RFLP method. To evaluate the possible effect of this polymorphism on gene expression, BCL-6 mRNA levels in nine FCL tumors with the 397G-G genotype and in nine FCL tumors with the 397G-C genotype were measured by quantitative real-time RT-PCR. The 397C polymorphic allele was found in 32 FCL cases (37.6%), in 20 controls (20.4%) and in 17 (18.9%) samples from the DNA Polymorphism Discovery Resource. The prevalence of the 397G-C and 397C-C genotypes was significantly higher in FCL cases than in control group (p = 0.01). No difference in BCL-6 gene expression was observed between FCL cases with 397G-G and 397G-C genotypes. The present study demonstrates a possible association between the 397C allele of the BCL-6 proto-oncogene and FCL. The similar levels of BCL-6 mRNA expression in 397G-G and in 397G-C FCL cases suggests that any possible oncogenic effect of the polymorphic allele would not simply be related to a direct effect on BCL-6 gene expression and suggests the existence of other FCL susceptibility genes that are in linkage disequilibrium with the 397C allele of the BCL-6 gene.

DNA-Binding Proteins↗