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A R Williams

Publications and source records attributed to A R Williams.

At least 19 recordsLinked to original sources

Effects of the putative 5-HT1A receptor antagonist NAN-190 on free feeding and on feeding induced by the 5-HT1A receptor agonist 8-OH-DPAT in the rat.

The effects of the putative 5-HT1A receptor antagonist NAN-190 on feeding and spontaneous locomotor activity in rats were examined. The drug elicited a robust, dose-dependent (0.01-10 mg/kg) increase in food consumption in free feeding animals. Microstructural analysis of feeding induced by NAN-190 (3 mg/kg) revealed that the drug increased the duration of feeding and number of feeding bouts but decreased the feeding rate. The increase in feeding induced by 3 mg/kg of NAN-190 was not apparent until 2-4 h after injection. This prolonged latency to onset of the feeding response appeared to be due to response competition. Thus, a 'neuroleptic-like' action of the drug on spontaneous motor activity was observed during the the initial 2 h following injection. A dopamine receptor antagonist action of NAN-190 was also indicated by the results of studies in which the drug was observed to block oral stereotypy induced by the dopamine receptor agonist apomorphine. In interaction studies, NAN-190 (0.1 and 10 mg/kg) failed to block the feeding response induced by the prototypical 5-HT1A receptor agonist 8-OH-DPAT (0.0625 and 1.0 mg/kg) and indeed, appeared to have an additive effect with 8-OH-DPAT on consummatory behaviour. These data suggest that NAN-190 may act as a partial agonist rather than an antagonist at the 5-HT1A receptor and also provide the first evidence that the drug has dopamine receptor antagonist properties in vivo.

8-Hydroxy-2-(di-n-propylamino)tetralin

Minimal deviation endometrioid adenocarcinoma of cervix: a clinicopathological and immunohistochemical study of two cases.

We describe the clinicopathological features of two cases of minimal deviation endometrioid adenocarcinoma of cervix. This is a rare tumour whose predominant pattern is one of bland endometrial-type glands infiltrating the cervical wall without a stromal response. Thus, it may be confused with benign conditions such as cervical endometriosis. The two cases demonstrate that this tumour may behave aggressively despite its bland appearances. An immunohistochemical study was performed and showed only focal reactivity of neoplastic glands for carcinoembryonic antigen, which would limit its diagnostic use in small biopsy specimens.

Adenocarcinoma

Nucleation and evolution of ultrasonic cavitation in a rotating exposure chamber.

The nucleation and progression of ultrasonic cavitation in a rotating exposure chamber were investigated by observing hemolysis of a 0.5% suspension of erythrocytes. Bursts of 1.6 MHz ultrasound beams of 11 W/cm2 spatial peak intensity were synchronized with the rotation to aim the bursts down the axis of a cylindrical chamber. Cavitational hemolysis always occurred in fresh phosphate buffered saline (PBS) solution, but cavitation incidence declined to 38% in 4 day old PBS. The amount of hemolysis for 11 ms or 44 ms bursts with 60 rpm rotation increased in proportion to the number of bursts. Hemolysis was found above a minimum burst duration of 5.5 to 8.3 ms in the normal 2 cm chamber. This did not appear to change for 1 cm or 4 cm chamber lengths, but it did change to about 2.2 ms and about 44 ms for over- and undersaturated gas conditions, respectively. Off-times associated with rotation speeds of 15 to 30 rpm reduced the effectiveness of the cavitation, and addition of fixed cells at only 0.01% to 0.02% greatly reduced the hemolysis. For this ultrasonic exposure system, several thousand bubbles, possibly generated from as few as one cavitation nucleus, move across the chamber at up to 10 m/s, each lysing a few hundred cells, and then are cycled back to the front of the chamber by the rotation to reinitiate the cavitation on the next burst.

Air

Imaging microbubbles and tissues using a linear focussed scanner operating at 20 MHz: possible implications for the detection of cavitation thresholds.

B-Scan images have been used as a means of detecting the onset of cavitation in tissues. New echoes appearing during simultaneous sonication with therapeutic ultrasound have often been attributed to bubble formation. In this study temperature rises up to 15 degrees C W-1 cm2 in guinea pig leg (post-mortem) were found, which would itself increase the rate of growth of gas bubbles. It is also hypothesized that a temperature dependent attenuation coefficient predicted by Bamber and Hill may, at least in part, account for new echoes appearing in tissues. Possible artefactual echoes in the B-scan images arising from acoustically induced gas bubbles in the coupling medium are also discussed.

Animals

Measurement of cavitational activity within ultrasonic baths.

The formation of free iodine from the KI/CCl4 chemical dosimeter has been used to quantify the amount of cavitational activity occurring within a 25 kHz cleaning bath under various exposure conditions. The amount of activity occurring within the bath was related to the supply voltage to the cleaning bath, the time of exposure and the volume of solution. An important observation was that the amount of cavitational activity occurring within a glass beaker suspended within a water-filled bath varied by as much as a factor of ten if that beaker contained different volumes of the test solution. Also, the amount of cavitation occurring within the exposure vessel and its contents of an ultrasonic cleaning bath will assist in the cleaning of dental instruments and their accessories.

Carbon Tetrachloride

Mechanisms for hemolysis by ultrasonic cavitation in the rotating exposure system.

The rotating chamber provides a useful system for enhancing cavitation bioeffects so that they may be more easily studied. A tube with acoustically transparent windows was rotated at 72 rpm perpendicular to its axis. The 1.61 MHz ultrasound beam was switched on and off in 42 ms bursts to expose the chamber while it was aligned with the beam. The hemolysis of 0.5% suspensions of canine erythrocytes was used as a measure of the efficacy of this rotating exposure system. Use of dialysis membrane, agar plugs, plastic sealing film or wax film for the windows produced no differences in the results for exposure intensities above an apparent threshold of 2-2.8 W/cm2, up to 16 W/cm2, at which essentially 100% lysis was observed. Changing the tube length from 1.4 cm to 4 cm, or partitioning it into three 0.5 cm segments had little influence on the results, but a short 0.5 cm chamber had reduced efficacy. Pressurizing the suspension filled chamber at 10 MPa to reduce the population of cavitation nuclei reduced the hemolysis. Separately pressurizing the suspension or the chamber produced indistinguishable, smaller reductions in hemolysis. The results lead to the hypothesis that the hemolysis occurs primarily in the bulk of the medium (rather than on surfaces). Bubbles recycled by rotation into the medium move toward the back of the chamber at estimated speeds of 10 m/s, generating hydrodynamic stresses sufficient to cause the observed hemolysis.

Acoustics

Genetic effects for reproductive traits in beef cattle and predicted performance.

Reproductive data were collected on 4,595 cow exposures and subsequent calvings over four generations in a rotational crossbreeding study involving Angus, Brahman, Charolais and Hereford breeds. Direct and maternal additive (Ig and Mg) and nonadditive (Ih and Mh) genetic effects were estimated for calving rate, calf survival, weaning rate, calving assistance and calf birth date. Genetic effects were estimated by regressing individual animal response on the proportion of genes from breed of origin and gene combinations expected for the four breeds in offspring and in dams. Breed direct and maternal additive and nonadditive genetic effects were expressed as a deviation from the least squares mean. Brahman Ig effects decreased calving and weaning rate (-9.5 +/- 4.0 and -11.8 +/- 4.4%) but Mh effects for weaning rate that included Brahman were positive, ranging from 16.5 +/- 6.7% for Angus-Brahman to 27.8 +/- 6.9% for Brahman-Hereford. The Brahman Ig effect delayed calf birth date (9.8 +/- 2.1 d; P less than .01), whereas Angus and Hereford Ig effects influenced earlier calf birth dates (-4.3 +/- 1.9 and -4.1 +/- 1.9 d; P less than .05). Brahman combination Mh effects also influenced earlier calf birth dates (P less than .01). The Charolais Ig effect for calving assistance was positive (4.3 +/- 1.9%; P less than .05), whereas Angus-Brahman and Brahman-Charolais Mh effects for calving assistance were negative (-6.5 +/- 3.2 and -7.0 +/- 3.2%; P less than .05) and more desirable. Predicted reproductive traits for rotational mating systems were intermediate between predicted reproductive traits for two- and three-breed terminal crosses. Predicted calving and weaning rates were maximized when Brahaman first-cross and Charolais-Hereford cows were used in three-breed cross mating systems.

Animal Husbandry

Immunohistochemical demonstration of altered intracellular localization of the C-Myc oncogene product in human colorectal neoplasms.

The distribution of the c-myc oncogene product p62 was examined by immunohistochemistry using the monoclonal antibody Mycl-9E10 in a series of 50 colorectal resections for carcinoma. The specimens were specially handled to ensure rapid fixation in formalin, and a significant improvement was shown in the quality and localization of staining compared with routinely handled specimens. Non-neoplastic mucosa showed the presence of nuclear staining of epithelial cells in 93 per cent of the samples, whilst all carcinomas showed cytoplasmic staining and infrequent nuclear staining. Adenomas showed an intermediate pattern, with significantly more frequent cytoplasmic distribution than non-neoplastic mucosa, but less than carcinomas. The results show that whilst fixation conditions are important in the immunolocalization of the c-myc protein product, there may be a consistent difference between non-neoplastic mucosa and carcinoma in the manner of association of p62 with the nucleus.

Carcinoma

Phonophoresis: an in vivo evaluation using three topical anaesthetic preparations.

An electrical sensory perception threshold technique has been developed for use with human volunteers. This technique has been used to reproducibly quantify the effects of three different commercially available topical anaesthetic preparations on superficial sensory cells (nociceptors) in the skin. Low intensities (0.25 W cm-2 SATA) of 1.1 MHz ultrasound had no detectable effects upon the rate of penetration of either one of the three anaesthetic preparations through human skin under conditions where temperature increases had been minimized.

Administration, Cutaneous

Positive and negative effects of diagnostic intensities of ultrasound on erythrocyte blood group markers.

Human erythrocytes were exposed in vitro to diagnostic intensities of ultrasound. Various antigenic tests were conducted to see if the different blood group markers had been changed. No change was observed following sonication for Ss, M, K1, ABO, and the rhesus factors. However a marked reduction was found for the N antigen when assayed using the lectin isolated from Vicia graminea. Several experiments were performed to ensure that this effect was not an artefact. If the cells were not resuspended in fresh medium immediately following sonicating then the magnitude of the effect rapidly decreased. We were unable to detect free N antigen in the supernatants from the sonicated cell suspensions. We were also unable to demonstrate changes in the level of the N antigen following sonication if we used anti-N sera from rabbits. A surprising observation was that different batches of the lectin preparation from the same manufacturer could eliminate the effect.

ABO Blood-Group System

Identification of mechanisms responsible for fetal weight reduction in mice following ultrasound exposure.

This study challenges existing interpretations of the effects of ultrasound on fetal development. The results demonstrated that a lower mean fetal weight in mice observed after intrauterine exposure to 2 MHz ultrasound resulted from maternal distress, and was not simply a direct effect of ultrasound interaction with the fetuses. At day 8 of gestation continuous wave ultrasound was applied to different regions of the maternal abdomen at spatial average intensities between 0.5 and 5.5 W cm-2 for 3 min. Insonating the uterus directly resulted in resorptions, abortions and gross developmental abnormalities, with rare instances of fetal weight reduction which were apparently associated with maternal distended bladder syndrome (DBS). When the ultrasound beam deliberately avoided the uterus, by a dorsal approach centred on the vertebral column, mean fetal weight at day 18 was significantly lower in all mothers showing DBS. Fetuses of insonated mothers not affected by DBS were not significantly different from the sham-insonated group whether the uterus was directly exposed or not. The fetal weight reduction endpoint was therefore found to be more closely correlated with maternal damage (DBS) than with ultrasound intensity.

Abdomen

Effects of ultrasound on placental transfer during the last third of gestation in the rat.

The effect of ultrasound on placental transfer in the rat has been measured in vivo. At 15, 18, 21 and 22 days of gestation one uterine horn of each anaesthetized rat was exposed, after laparatomy, to ultrasound. The control horn was effectively shielded. Radio-labelled tracers were then injected into the maternal circulation via a jugular vein cannula and fetuses removed simultaneously from both experimental and control horns at times predetermined to ensure minimal backflux from fetus to mother. Samples of maternal plasma were also taken at suitable intervals. The radioactive content of fetuses and plasma were measured and a unidirectional materno-fetal clearance value (Kmf) for each fetus calculated. It was shown that in rats whose body temperature was accurately maintained at 37 degrees C, ultrasound at the level used in the present study had no effect on placental clearance. However, in rats whose body temperature was allowed to fall to 32 degrees C, a 3 min exposure to 1.1 MHz continuous wave ultrasound at 1 W cm-2 caused a significant (p less than 0.001) decrease in the placental clearance of 22Na (by 55%) and 51Cr-EDTA (by 45%) in rats at 15 days of gestation. These effects showed no dose response and were not observed in rats at any of the other stages of gestation which we investigated. However, in rats at 21 days of gestation the clearance of 45Ca2+ was significantly (p less than 0.01) reduced (by 30%) by a similar exposure to ultrasound. It is concluded that although an interesting biological effect of ultrasound at low body temperatures has been observed, it has little relevance for the normal use of ultrasound in obstetrics.

Animals