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Biomedical subjects

A T Williams

Publications and source records attributed to A T Williams.

At least 37 records · Page 2Linked to original sources

Tibial realignment by oblique wedge osteotomy. A new method based on accurate measurement.

A new method for calculating the angle of correction in upper tibial osteotomies is described. The wedge differs from the current techniques in being oblique. The apex is sited on the medial cortex to lie level with the tibial tubercle. The wedge is coned downwards at an angle of 45 degrees, based laterally. This keeps clear of the bifurcation of the popliteal artery, whilst still being contained in the cancellous zone. The method of accurately determining the angle of the wedge and the width of the base using logarithmic calculations is outlined. Being oblique, on removal of the wedge, the cut surfaces match as they meet. Two screws are inserted to lie at right angles to the plane of osteotomy. A long leg plaster cast is worn for six weeks. Thereafter a cast brace is substituted to permit knee and ankle movements. The osteotomy unites rapidly across the large oblique contact surfaces. Pain relief has been substantial and lasting in every patient. The range of flexion returned to the level elicited under anaesthesia immediately prior to the operation.

Ankle↗

Ovarian gonadotropin-releasing hormone-like protein(s): demonstration and characterization.

Both GnRH and prostaglandin F2 alpha inhibit LH-stimulated cAMP accumulation and progesterone secretion in isolated luteal cells. Moreover, since ovarian GnRH receptors have been demonstrated, this study was conducted to determine if GnRH-like substances were present in the luteinized rat ovary. Detection of GnRH-like activity was based on a sensitive and specific ovarian membrane GnRH radioreceptor assay and an immunoassay specific for GnRH. Ovaries were extracted with an aqueous medium containing formic acid, HCl, trifluoroacetic acid, and NaCl. Material present in the supernatant fraction which adsorbed to Waters C18 Sep-Paks was subsequently eluted with acetonitrile and lyophilized. The redissolved ovarian extract showed substantial radioreceptor activity, but very little immunoassayable activity. The GnRH-like activity of the ovary was sensitive to proteolytic enzyme digestion and to incubations at 50 C for as little as 5 min, had an apparent mol wt greater than 1,000 but less than 10,000, and was not soluble in ether. Extracts of plasma did not exhibit radioreceptor or immunoreactive activity, whereas hypothalamic extracts exhibited both radioreceptor and immunoreactive activities. Liver and kidney extracts showed less radioreceptor activity than ovarian extracts and very little immunoreactive activity. Two peaks of radioreceptor activity appeared when the ovarian extract was further fractionated by reverse phase HPLC. The two peaks of GnRH-like activity were clearly separated from GnRH or [D-Ala6, des-Gly10] GnRH ethylamide, an analog used in this study, when these were included in ovarian extracts. It is concluded that rat ovaries contain a GnRH-like protein(s) with membrane binding properties similar to those of GnRH but with other characteristics distinctly different from those of GnRH. The ovarian GnRH-like protein is immunologically different from GnRH, sensitive to elevated temperatures which do not effect GnRH, and chromatographically different from GnRH during reverse phase HPLC.

Animals↗

The effect of horizontal differential prism on the binocular contrast sensitivity function.

The photopic binocular contrast sensitivity function is measured using a two-way resolution choice sinusoidal-grating target with horizontal differential prism before the right eye of one subject (AHT). A significant drop in sensitivity occurred with 3 prism-dioptres base-out or 4 prism-dioptres base-in prism at an observation distance of 5.9 m, and with 2 prism-dioptres base-out or 8 prism-dioptres base-in at 50 cm. An equivalent effect was confirmed with three additional subjects at a test distance of 2 m. The relationship between these results, the passive position, and the fusional reserves is discussed and reference is made to the effect of vertical differential prism.

Form Perception↗

The effect of vertical differential prism on the binocular contrast sensitivity function.

The binocular contrast sensitivity function is measured using horizontal sinusoidal gratings with base-down prism before the right eye. In photopic conditions one prism-dioptre causes a significant drop in sensitivity at all spatial frequencies and in mesopic conditions as little as a half prism-dioptre has a similar effect. The implications for a physiological tolerance for unintended vertical differential prism in spectacles are discussed.

Adaptation, Ocular↗

Calcium is an inhibitor of luteinizing hormone-sensitive adenylate cyclase in the luteal cell.

Both prostaglandin F2 alpha (PGF2 alpha) and LHRH inhibit LH-stimulated cAMP accumulation and progesterone secretion in the intact luteal cell, but have no effect on LH-sensitive adenylate cyclase activity in isolated membranes. The present studies were conducted to assess the possibility that calcium (Ca2+) may mediate the inhibitory activity of PGF2 alpha and LHRH in the rat luteal cell. Removal of extracellular Ca2+ significantly enhanced cAMP accumulation in response to LH by about 2-fold, but blunted LH-stimulated progesterone secretion. Incubation of luteal cells with A23187 caused a highly significant and dose-related decrease in LH-stimulated cAMP accumulation with a concentration for half-maximal inhibition (IC50) of about 1 microM. No effect of A23187 was seen on LH-sensitive adenylate cyclase activity, but the ionophore elicited significant inhibition of LH-stimulated intracellular cAMP accumulation in the presence of isobutyl-methylxanthine (MIX), a phosphodiesterase inhibitor. Inhibition by A23187 was Ca2+ dependent, since a decrease in extracellular Ca2+ to less than 100 microM completely blocked the effect of the ionophore. A23187 also significantly inhibited LH-stimulated progesterone secretion in response to LH or cholera toxin and inhibited cholera toxin-stimulated cAMP accumulation in the absence or presence of MIX. In incubations of isolated luteal membranes, Ca2+ produced a dose-dependent inhibition of LH-stimulated adenylate cyclase activity in the absence or presence of MIX at free Ca2+ levels between 5-20 microM (IC50, approximately 10 microM). Depletion of extracellular Ca2+ had no effect on inhibition of LH-stimulated cAMP accumulation by PGF2 alpha in the intact cell, and the inhibitory activity of LHRH was slightly reduced, but not abolished, by depletion of extracellular Ca2+. Verapamil, a Ca2+ channel blocker, had no effect on inhibition of LH-stimulated cAMP accumulation by PGF2 alpha or LHRH. It is concluded that an acute increase in intracellular Ca2+ inhibits activation of adenylate cyclase by LH in the rat luteal cell. This conclusion is based on studies that showed enhanced cAMP accumulation by LH in Ca2+-depleted media, Ca2+-dependent inhibition of LH-stimulated cAMP production by a Ca2+ ionophore, and direct inhibition of LH-sensitive adenylate cyclase activity by Ca2+ in luteal membranes. It is suggested that a similar effect occurs in response to PGF2 alpha or LHRH in the luteal cell, but inhibition by these luteolytic agents is not dependent on an influx of extracellular Ca2+, but, rather, is due to an increase in intracellular Ca2+ by other mechanisms.

Adenylyl Cyclases↗

Calmodulin-dependent glycogen synthase kinase: identification in liver of normal and phosphorylase kinase-deficient rats.

We have purified a calmodulin-dependent glycogen synthase kinase from livers of normal and phosphorylase kinase-deficient (gsd/gsd) rats. No differences between normal and gsd/gsd rats were apparent in either (a) the ability of liver extracts to phosphorylate exogenous glycogen synthase in a Ca2+- and calmodulin-dependent manner or (b) the purification of the calmodulin-dependent synthase kinase. Although extracts from rat liver, when compared to rabbit liver extracts, had a significantly reduced ability to phosphorylate exogenous synthase, the calmodulin-dependent synthase kinase could be purified from rat liver using a protocol identical to that described for rabbit liver. Moreover, the synthase kinase purified from rat liver had properties very similar to those of the rabbit liver enzyme. The enzyme was completely dependent on calmodulin for activity against glycogen synthase, was unable to phosphorylate phosphorylase b, catalyzed the rapid incorporation of 0.4 mol phosphate/mol of glycogen synthase subunit, selectively phosphorylated sites 1b and 2 in the glycogen synthase molecule, had a Stokes' radius of about 70 A, and appeared to be composed of subunits of Mr 56,000 and 57,000. These observations led us to conclude that (1) calmodulin-dependent glycogen synthase kinase is distinct from other kinases previously described and (2) the rat liver kinase and the rabbit liver kinase are very similar enzymes.

Animals↗

Purine modulation of LH action in gonadal cells.

A rapid and marked amplification of LH and FSH-stimulated cyclic AMP accumulation and steroid secretion is produced by adenosine in luteal and granulosa cells, respectively, of both the rat and the human ovary. The rat Leydig cell response to LH, however, was unaffected by adenosine. In the luteal cell, adenine nucleotides and adenosine were equipotent with decreasing activity shown by inosine, adenine and hypoxanthine--guanosine, guanine, xanthine and pyrimidines were inactive. Both an extracellular and intracellular site appears to be involved in adenosine amplification of LH--the extracellular site accounted for about 20% of the response and may be a catalytic receptor site. The intracellular site was directly related to an increase in luteal cell ATP levels in which adenosine appears to serve as a selective prosubstrate for hormone activated adenylate cyclase. The luteal antigonadotropic action of PGF2 alpha was blocked by adenosine and these modulators were shown to be competitive antagonists of LH-stimulated cyclic AMP accumulation. Due to the ubiquitous nature of both adenosine and PGF2 alpha, (conditions have been described in other systems for their rapid release,) it is suggested that they may serve as important local humoral modulators of gonadotropin action for regulation and control of ovarian function.

Adenosine↗

Rapid, specific method for diethylstilbestrol analysis using an in-line photochemical reactor with high-performance liquid chromatography and fluorescence detection.

Low ppb levels of diethylstilbestrol in biological samples of human and animal origin can be determined using a unique in-line separation-photoreaction-fluorescence detection analytical system. After a very simple extraction procedure, the diethylstilbestrol is separated from interfering substances by high-performance liquid chromatography, photoconverted to a fluorescent product, and detected by fluorescence spectroscopy at optimised excitation-emission wavelengths. A sample can be extracted and analysed in less than 1 h.

Animals↗

The contribution of gonadostatin (inhibin-F) to the control of gonadotropin secretion in a simulated estrous cycle in steroid-treated ovariectomized rats.

We have examined the contribution of gonadostatin to the control of gonadotropin secretion throughout the rat estrous cycle. The estrous cycle was simulated in rats ovariectomized on diestrus-1, designated day 1 (D-1) by use of low or high level estradiol and progesterone Silastic implants. The steroid implant regimen simulated the major changes of these hormones in the blood during the course of the estrous cycle. Injections of porcine follicular fluid (pFF) were superimposed on this steroid regimen. Four treatment combinations of steroid and pFF or their controls were tested: 1) steroid implants only, 2) pFF only at a constant dose level, 3) steroid implants and pFF injections at a constant dose level, and 4) steroid implants and pFF injections with reduced levels on simulated proestrus. In group 1 both basal and surge release of LH were similar to those in the intact rat, but both basal and surge release of FSH were significantly elevated above levels observed in the intact rat for the respective periods. In group 2 FSH was suppressed to diestrous levels throughout the course of the experiment, with no surge occurring on D-3. Serum LH levels were slightly elevated above diestrous levels (50-150 ng/ml) with no surge. In group 3 serum levels of both gonadotropins were suppressed to diestrous levels on D-1 and D-2, and a steroid-induced, pFF-attenuated surge occurred on the afternoon of D-3. Group 4 had, with a minor variation, proestrous-like FSH and LH surges on D-3 and basal (diestrous) gonadotropin levels during simulated D-1, D-2, and early proestrus. This study supports previous evidence for estradiol and progesterone control of LH secretion and elaborates the control of FSH secretion. The role of gonadostatin and steroids is demonstrated in the negative feedback regulation of FSH secretion.

Animals↗

Inner-city community health centre: six years' experience.

Some aspects of the work of an inner-city community health centre administered by a large teaching hospital are described. Some sociodemographic characteristics and patterns of morbidity of persons attending the centre over the past six years are presented. Initial attempts of evaluation of clinical services provided by the centre are described.

Adolescent↗

Prevalence of alcoholism in a Sydney Teaching Hospital: some aspects.

This paper presents some preliminary findings from an epidemiological study of inpatients in Royal Prince Alfred Hospital in 1977. The sample included 457 patients. Of these, 15% were found to have alcohol-related reasons for admission to hospital, and 33% had concomitant alcohol problems. The drinking habits of 30% of males and 9% of females placed them at risk. Some commonly used laboratory tests are evaluated.

Adolescent↗

Osseous choristoma of the choroid simulating a choroidal melanoma. Association with a positive 32P test.

We report the clinical and histopathologic features of an osseous choristoma of the choroid that appeared in a 26-year-old woman. Her diagnostic evaluation included a radioactive phosphorus (32P) uptake test, which was 270% positive and led us to believe that the lesion was an atypical malignant melanoma. The extent of true ossification within this tumor, seen microscopically, explains the false-positive uptake of radioactive phosphorus by this benign tumor; it is well known that bone avidly accumulates radioactive phosphorus. We recommend that all "atypical choroidal melanomas" be studied for the presence of bone, with bone-free roentgenograms, ultrasonography, and possibly, computerized tomographic scans before 32P testing or enucleation. This, to our knowledge, is the second histopathologically proved case of an osseous choristoma of the choroid to be reported in the literature.

Adult↗