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Biomedical subjects

C D Jones

Publications and source records attributed to C D Jones.

At least 127 records · Page 7Linked to original sources
PubMed1990

Estrogen synthetase inhibitors. 2. Comparison of the in vitro aromatase inhibitory activity for a variety of nitrogen heterocycles substituted with diarylmethane or diarylmethanol groups.

The preparation and in vitro aromatase inhibitory activity of a wide variety of heterocyclic (4,4'-dichlorodiphenyl)methanes and -methanols are described. The choice of the two diaryl-bearing moieties as a vehicle for the evaluation of the heterocycles was made by the comparison of series of imidazole and pyridine-derived compounds with similar pyrimidine compounds reported previously. A structural model for the most active compounds is also presented. The activity of a related series of the compounds which contain two heterocyclic moieties was found to be consistent with the model. Many of the compounds evaluated, including representatives of the pyridine, imidazole, pyrimidine, pyrazole, triazole, thiazole, and isothiazole classes, exhibit EC50 potencies for aromatase inhibition at low nanomolar levels. These compounds are at least as potent as other nonsteroidal aromatase inhibitors reported previously.

Androstenedione↗
PubMed1990

An evaluation of a solid phase red cell adherence test for detecting platelet-associated IgG in immune thrombocytopenia.

A solid phase red cell adherence (SPRCA) test, designed for platelet cross-match testing, was evaluated to determine its efficacy in detecting platelet-associated IgG (PAIgG) in immune thrombocytopenic purpura (ITP). This new method was compared to the platelet suspension immunofluorescence (PSIF) test. Fifty-three patient samples were tested by both methods, including 17 for whom a clinical diagnosis of ITP had been made. The SPRCA method showed 65% sensitivity, whereas the PSIF method showed 53% sensitivity. The specificity for both was 100%. The SPRCA compared favorably to the PSIF test in sensitivity and cost effectiveness. The SPRCA test is rapid, easy to perform, and suitable for detecting PAIgG in ITP.

Blood Platelets↗
PubMed1990

A whole body transportable indirect calorimeter for human use in the tropics.

A transportable, whole body indirect calorimeter, designed for use in the tropics, is described. The calorimeter was built to study energy expenditure of people having chronically or acutely low levels of food intake, and it will help to determine energy adaptations made by individuals with restricted food intake. The calorimeter comprises two units: a 27 m3 ventilated chamber connected to an office housing control and monitoring equipment. The system also allows the experimenter to assess the rate of energy expenditure by means of a ventilated hood or a baby respiration chamber. The incoming air flow rate is variable and is typically set at approximately 30 l/min. Carbon dioxide production (VCO2) and oxygen consumption (VO2) are continuously monitored by means of differential gas analysers via a computerized data acquisition unit. Gas production/consumption rates are measured with a delay of 80 s, the complete response to step changes in VCO2 or VO2 consumption being calculated over 15 min using the rate of change terms in the gas exchange equations. The total electrical power required for the whole system is 12 kW. The calorimeter has been functioning for nearly 4 years in a rural village of The Gambia during which ambient temperatures have ranged from 16 to 44 degrees C and dewpoints from -8 to 24 degrees C. The performance and accuracy of the calorimeter were tested using 20 per cent CO2 in N2 infusion and butane burning. Agreement between the theoretical and the measured values was found to be 99 per cent for VO2 and 100 per cent for VCO2 with a precision for both gases of +/- 10 ml/min over a 1-h period.

Calorimetry, Indirect↗
PubMed1989

Antagonism of androgen and estrogen effects in guinea pig seminal vesicle epithelium and fibromuscular stroma by keoxifene (LY156758).

Using separated epithelium (SVE) and fibromuscular stroma (SVM) of guinea pig seminal vesicle, the antihormonal effects of daily subcutaneous administration (14 and 28 days) of the benzothiophene keoxifene (LY156758; [6-hydroxy-2-(4-hydroxyphenyl)benzo(b) thien-3-yl] [4-(2-1-piperidinyl) ethoxyl] phenyl) methanone hydrochloride) in intact, castrate, and androgen/estrogen-maintained castrate animals was evaluated. The compound was devoid of agonist activity in castrated males, in that the compound had no stimulatory effect on SVM wet weight or DNA content. In vitro cytosolic binding of [3H]estradiol (E2) in the SVM was decreased in a concentration-dependent manner by keoxifene, but the compound did not perturb the binding of [3H]dihydrotestosterone (DHT) in the SVM or SVE. Likewise, keoxifene administration to castrated males treated with exogenous steroids antagonized the estrogen-induced hyperplastic response of the SVM, whereas no interference with androgen-induced growth of the SVM or SVE was observed. Keoxifene treatment of intact male guinea pigs produced regression of the androgen-sensitive SVE as well as the androgen/estrogen-sensitive SVM. Keoxifene-induced decreases in guinea pig serum testosterone levels were associated with this activity. Histological analysis of the seminal vesicle under these conditions suggests androgen deprivation. These findings indicate that keoxifene is a physiological antagonist of androgen action in the intact male guinea pig. The pure estrogen antagonist properties of keoxifene and its ability to decrease accessory sex organ epithelium and fibromuscular stroma in vivo suggest potential applications of the benzothiophenes in the medical management of prostatic neoplasia.

Androgen Antagonists↗
PubMed1987

Importance of measurement of spongious vertebral bone mineral density in the assessment of osteoporosis.

Quantitative computed tomography (QCT) measurements of bone mineral density, volume, and content were made of the spongious and compact portions of a vertebral body and of the total vertebral body in 19 osteoporotic patients (13 women and 6 men) and 20 normal (control) age- and sex-matched patients. Specifically, CT scans of 10mm thick transverse sections of L2 or L3 of each osteoporotic and control patient were subjected to QCT bone measurement with the use of K2HPO4 calibration for converting CT values into units (mg/ml) equivalent to bone mineral density. In every instance, a significant difference was found in the spongious vertebral bone mineral density (and content) between the osteoporotic and the paired normal groups. Even when the total vertebral bone mineral content was normal, the spongious vertebral bone mineral density was significantly less in the osteoporotic patients. Only in the osteoporotic men was a difference in compact bone density (and content) found; the osteoporotic men had a significantly lower compact bone mineral than did the normal male patients. This study shows that QCT can be applied to measurement of bone mineral density (and content) of both the anterior spongious and the more dense compact vertebral bone from a single section of a lumbar vertebra and that it is the anterior, spongious, vertebral bone rather than the compact vertebral bone that exhibits the more severe decrease in bone mineral density (and content) due to osteoporosis.

Adult↗
PubMed1987

Aromatase inhibition by 5-substituted pyrimidines and dihydropyrimidines.

The inhibition of estrogen biosynthesis has been suggested to be an effective treatment of hormone-dependent diseases, particularly breast cancer. Several series of 5-substituted pyrimidine derivatives have been synthesized and tested for their ability to inhibit the enzyme aromatase (estrogen synthetase). Compounds were evaluated in an in vitro assay that measured the inhibition of rat ovarian microsomal aromatase activity. Greatest inhibitory activity was achieved in the cases of diarylpyrimidinemethanols and diarylpyrimidinyl methanes which were substituted in the 4- and 4'-positions with electron-withdrawing substituents, particularly Cl.

Animals↗
PubMed1987

Clinical hypersensitivity to specific aerosol challenge in parenterally immunized calves.

This paper reports an experiment designed to demonstrate that the calf lung can be sensitized to a specific respirable challenge following parenteral immunization with a nonliving antigen (human serum albumin). The possibility that immune-mediated injury could subsequently interfere with nonspecific mucosal defenses was also investigated by infecting calves with Pasteurella haemolytica after the antigen challenge and assessing pulmonary clearance of the organism. The results indicated that specific aerosol challenge produces reversible signs of respiratory hypersensitivity and that persistence of incidental infection in the upper respiratory tract is potentiated. Since the calves were sensitized by an immunization regime which imitated conventional vaccination, this study highlights the potential dangers of inactivated parenteral respiratory vaccines.

Aerosols↗
PubMed1987

Proliferation of Pasteurella haemolytica in the calf respiratory tract after an abrupt change in climate.

Two groups of four calves were exposed to a poly-disperse aerosol of 1.3 X 10(4) to 16 X 10(4) colony forming units (CFU) of nalidixic acid resistant Pasteurella haemolytica type A1 litre-1 of air with a mass median aerodynamic diameter of 2.6 +/- 0.8 microns. One group of calves was kept at 5 degrees C, 72 per cent relative humidity (RH) and the second was subjected to an abrupt change in climate directly after aerosol exposure from 5 degrees C, 75 per cent RH to 13 degrees C, 84 per cent RH. Clearance of the organism from the respiratory tract of the calves was monitored over the subsequent 23 hours by a method of tracheal and nasopharyngeal swabbing. Clearance measured at the trachea in all calves in both groups was not a continuous, uninterrupted process but exhibited a temporary decline between eight and 14 hours. Calves subjected to an abrupt change in climate after aerosol challenge had raised respiratory rates eight to 14 hours later and P haemolytica proliferated in the nasopharynx over the entire 23 hours. There was no apparent effect of climate on P haemolytica in the trachea. It is suggested that rapid growth of P haemolytica accompanying a change in climate may be an important aetiological factor in pneumonic pasteurellosis of calves.

Animals↗
PubMed1987

Transmission of Pasteurella multocida in rabbits.

Contact and airborne transmission of P. multocida in rabbits was evaluated in an artificially controlled environment. Transmission by contact occurred more readily from rabbits with acute infections than from rabbits with chronic infections. However, airborne transmission to rabbits in adjacent cages did not occur.

Air Microbiology↗
PubMed1987

Deposition and clearance of radiolabelled monodisperse polystyrene spheres in the calf lung.

Two groups of three calves were exposed to monodisperse aerosols of radiolabelled polystyrene spheres measuring 3.3 microns in aerodynamic diameter (SD 0.3 micron). Although the spheres preferentially deposited in the trachea and major bronchi, 72 per cent of the total radioactivity deposited was found in lung tissue beyond the major bronchi. Mean alveolar deposition, estimated from the end retention value after mucociliary clearance, was 34 per cent in the group of bull calves and 52 per cent in the group of heifer calves. Alveolar deposition increased from 47 to 56 per cent (P less than 0.05) in heifer calves treated with oestradiol. Mucociliary clearance of the spheres was unaffected by repeated exposure to the experimental aerosol and the overall mean mucociliary clearance rate constant was 1.28 (+/- 0.43) h-1 (half-life 32 minutes). Clearance curve profiles tended to be characteristic for individual calves but variation in mucociliary clearance rates within calves was high and on occasions clearance rate inexplicably fell to 10 to 50 per cent of the maximum achievable value for the calf. Neither mucociliary clearance rate nor alveolar deposition was affected by a change in climate from 14 degrees C, 87 per cent relative humidity to 5 degrees C, 75 per cent relative humidity. Both alveolar deposition and mucociliary clearance of the spheres could be manipulated using a beta-adrenergic treatment.

Aerosols↗
PubMed1984

Antiestrogens. 2. Structure-activity studies in a series of 3-aroyl-2-arylbenzo[b]thiophene derivatives leading to [6-hydroxy-2-(4-hydroxyphenyl)benzo[b]thien-3-yl] [4-[2-(1-piperidinyl)ethoxy]-phenyl]methanone hydrochloride (LY156758), a remarkably effective estrogen antagonist with only minimal intrinsic estrogenicity.

In an effort to prepare nonsteroidal antiestrogens demonstrating greater antagonism and less intrinsic estrogenicity than those currently available, a series of 3-aroyl-2-arylbenzo[b]thiophene derivatives was synthesized. These compounds were prepared by Friedel-Crafts aroylation of appropriate O-protected 2-arylbenzo[b]thiophene nuclei with basic side-chain-bearing benzoyl chlorides followed by removal of the protective groups to provide the desired compounds containing both hydroxyl and basic side-chain functionality. A particularly useful method for the cleavage of aryl methoxy ethers without removal of (dialkylamino)ethoxy side chain functionality elsewhere in the molecule was found to be AlCl3/EtSH. The benzothiophene derivatives were tested for their ability to inhibit the growth-stimulating action of estradiol on the immature rat uterus. Seemingly minor changes in the side-chain amine moiety were found to have profound effects on the ability of the compounds to antagonize estradiol. Analogues having basic side chains containing cyclic (pyrrolidine, piperidine, and hexamethyleneamine) moieties were found to have less intrinsic estrogenicity and to antagonize estradiol action more completely than their noncyclic counterparts. The most effective antiestrogen in the series, compound 44, [6-hydroxy-2-(4-hydroxyphenyl)benzo[b] thien-3-yl]-[4-[2-(1-piperidinyl)ethoxy]phenyl]methanone, elicited a modest uterotropic activity that did not increase with increasing dose. In antagonism of estradiol, 44 exhibited a degree of inhibition surpassing that of tamoxifen at any dose tested. The new benzothiophene antiestrogen was also shown to have high affinity for rat uterine cycloplasmic estrogen receptor and to be an inhibitor of the growth of DMBA-induced rat mammary tumors.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1984

Relationships between counts of nasopharyngeal bacteria, temperature, humidity and lung lesions in veal calves.

Nasopharyngeal swabs were taken from four groups of veal calves at intervals throughout their growth and the aerobic bacteria cultivated from the swabs counted. The calves were kept under three different husbandry systems; naturally ventilated straw-yards, fan-ventilated crates and crates with a controlled climate. The numbers of bacteria isolated varied in a complex manner; however, in one group of calves a significant proportion (P less than 0.01) of the variation in weekly bacterial counts was associated with the changes in vapour pressure and temperature which took place between two and four days previously. In calves kept at a constant temperature of 16 degrees C, the bacterial populations in the nasopharynx were at a minimum between 65 and 75 per cent relative humidity and tended to rise at humidities outside this range. There was a temporal relationship between nasopharyngeal bacteria and lung lesions. In three groups the numbers of bacteria in calves at nine weeks old were positively correlated (P less than 0.05) with lung damage observable at 16 to 18 weeks old.

Animals↗
PubMed1983

Effects of a new antiestrogen, keoxifene (LY156758), on growth of carcinogen-induced mammary tumors and on LH and prolactin levels.

Keoxifene (LY156758) is a new benzothiophene-derived antiestrogen with an extremely low degree of estrogenicity. Administration of 1-20 mg/kg per day inhibited the growth of 7, 12-dimethylbenzanthracene (DMBA)-induced mammary tumors in rats. The degree of inhibition of mammary tumor growth was similar to that observed with tamoxifen treatment.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1983

Antagonism of estrogen action with a new benzothiophene derived antiestrogen.

A new benzothiophene derived antiestrogen, LY139481, inhibited the uterotropic action of estradiol in a dose related fashion, and at 1 mg per day suppressed more than 90 percent of estradiol's activity in immature rats. LY139481 induced minimal uterotropic activity, and that activity declined in relation to dose. The relative binding affinity of LY139481 for rat uterine cytosol estrogen receptors was greater than that of estradiol in competitive assays and increased in relation to temperature (2.9 +/- 0.5 x estradiol at 30 degrees C). LY139481 caused estradiol-induced uterine hypertrophy to regress in a manner similar to that which resulted from withdrawal of estradiol treatment. Three successive daily injections of LY139481 slightly increased uterine weight, and blocked additional uterotropic action in response to estradiol and LY139481 administration on subsequent days. Furthermore, ten daily injections of estradiol alone did not increase uterine weight in animals pretreated with LY139481 for three days. In contrast, LY139481 did not prevent the partial uterotropic action of tamoxifen administration.

Animals↗
PubMed1983

Antifertility effects of tetradecyl sodium sulphate in rabbits.

Acrosin and acrosomal hyaluronidase were inhibited by tetradecyl sodium sulphate (TDSS) in vitro at concentrations of less than 10(-4) M. TDSS prevented the removal in vitro of the cumulus oophorus by testicular hyaluronidase and the zona pellucida by acrosin. TDSS had a contraceptive effect in rabbits when administered intravaginally before coitus or released at levels of 1-3 micrograms/day from intrauterine silicone rubber devices.

Acrosin↗