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J M Williams

Publications and source records attributed to J M Williams.

At least 91 records · Page 5Linked to original sources
PubMed1999

A reporter gene assay to assess the molecular mechanisms of xenobiotic-dependent induction of the human CYP3A4 gene in vitro.

1. A plasmid containing 1 kb of the CYP3A4 regulatory (promoter) region coupled to a reporter gene for secretary placental alkaline phosphatase (SPAP) was transfected into HepG2 cells. Transfected cells were dosed with several known inducers of CYP3A4 and the levels of SPAP were measured. The effect of co-transfecting a plasmid encoding the human glucocorticoid receptor on reporter gene activity was also examined. 2. Dexamethasone induced CYP3A4-dependent reporter gene expression in a concentration-dependent manner and induction was approximately doubled in the presence of the glucocorticoid receptor. Dexamethasone-dependent induction was blocked by RU-486 (a glucocorticoid receptor antagonist), in the presence of the co-transfected glucocorticoid receptor. 3. Induction of CYP3A4-dependent reporter gene expression and enhancement of the induction by the glucocorticoid receptor was also observed with pregnenolone-16alpha-carbonitrile (PCN), rifampicin, phenytoin, carbamazepine, phenylbutazone and phenobarbitone, all known in vivo inducers of CYP3A4 in man. 4. Metyrapone and sulfinpyrazone induced CYP3A4-dependent reporter gene expression, but induction was not enhanced by the glucocorticoid receptor. 5. Clotrimazole, erythromycin and triacetyloleandomycin (TAO) did not induce CYP3A4-dependent reporter gene expression, consistent with the observation that these inducers act through post-transcriptional mechanisms. 6. These results highlight differences in the molecular mechanisms of induction of CYP3A4 by the xenobiotics studied and indicate that the glucocorticoid receptor is involved in the induction of the CYP3A4 gene by some, but not all, CYP3A4 inducers. 7. We propose that the approach described here provides a useful in vitro approach for the identification of transcriptional regulators of the CYP3A4 gene.

Alkaline Phosphatase↗
PubMed1999

Athletic injury, psychosocial factors and perceptual changes during stress.

In this study, we measured changes in state anxiety, visual perception and reaction time during stress among 196 collegiate athletes participating in 10 sports. The athletes also completed measures of life events and social support at the beginning of their seasons. Measures of life events stress, social support, perceptual changes and changes in reaction time during stress were used as predictors of the number of injuries. For the entire sample, the only significant predictor of injury was negative life events stress (R = 0.45, P < 0.001). Following the suggestions of Smith et al., simple correlations were performed for those with least social support (bottom 33%, n = 65). Among this group, those individuals with more negative life events and greater peripheral narrowing during stress incurred more injuries than those with the opposite profile. Our findings are in line with the model of Andersen and Williams, in that those individuals who were low in a variable that buffers stress responsivity (i.e. social support), their negative life events and peripheral narrowing under stress (large and medium effect sizes, respectively) were substantially related to their number of injuries.

Adult↗
PubMed1999

The effect of imageability and predicability of cues in autobiographical memory.

Four experiments investigated the role of imagery in the recollection of autobiographical memories. The first two experiments examined the effects of word imageability and word frequency on the retrieval of personal memories in a cued autobiographical memory task. They showed that the imageability of cues (but not frequency) mediates specificity in the recall of personal memories. Experiment 2 explored how different imagery modalities (visual, olfactory, tactile, auditory, and motor) influence autobiographical retrieval. Consistent with research on imagery modalities in verbal learning paradigms, visual imageability emerged as the most significant predictor of specificity. Experiments 3 and 4 examined how far a knowledge-based account of imagery effects might account for these effects, using predicability as a measure of semantic richness of a cue. Results found that visual imageability of cues accounted for more variance in specificity of recall than did predicability. The results are explained in terms of the way images represent the most efficient form of summarizing the information that can be used at each stage of the recollection process: setting the retrieval plan, strategic search, and evaluation of candidate episodes.

Adult↗
PubMed1999

Effects of hyaluronic acid on cartilage degradation.

Based on the published literature available so far, it appears that naturally derived hyaluronic acid (HA) and newer formulations available on the market belong to the pharmacologic class of slow-acting drugs for the treatment of osteoarthritis. These compounds seem to have the potential to modulate the painful symptoms of osteoarthritis as well as to improve the function of the osteoarthritis joint. Positive clinical consequences are based on direct and indirect effects of viscosupplementation associated with a normalization of the rheologic properties of the osteoarthritic synovial fluid, decreased inflammation, and end-coating of the pain receptors in the osteoarthritis joint. Few in vivo data exist in humans to support the concept that HA formulations could have a structure-modifying effect on human osteoarthritis cartilage. Animal-based studies have demonstrated positive effects of exogenous HA on pain in the joint, heat shock proteins, and in models of osteoarthritis. Although many promising effects of exogenous HA have been reported, there remains uncertainty as to the effectiveness of reversing cartilage injury and other manifestations of joint diseases with exogenous HA because of difficulties in interpreting and unifying results of these studies. This is due largely to differences of cartilage source in models of joint/cartilage injury, multiple end points, the controls employed, analytical techniques, and the molecular weight of exogenous HA used. There exists a need for uniform agreement as to the choice of injury model, time points of the study, evaluation tools, and source and molecular weight of the HA used if we are to determine whether exogenous application of HA has a truly beneficial role in the reversal of cartilage injury.

Animals↗
PubMed1999

New technologies for diagnosing and monitoring glaucomatous optic neuropathy.

BACKGROUND: Recently, instruments have been developed to provide real-time, quantitative measurements of the optic disc and retinal nerve fiber layer (RNFL) for use in glaucoma management. Our objective is to (1) provide an overview of two of these instruments, the confocal scanning laser ophthalmoscope (Heidelberg Retina Tomograph, HRT) and scanning laser polarimeter (Nerve Fiber Analyzer, NFA) and (2) compare measurements obtained with these instruments to clinical features used in the diagnosis of glaucoma. METHODS: Twenty glaucoma patients, 4 normal subjects and 20 glaucoma subjects were included. All subjects had images obtained with the HRT and NFA, and RNFL and optic disc photography completed within 5 weeks of each other. The HRT results were compared with qualitative evaluation of stereophotographs of the optic disc, and NFA results were compared against a semi-quantitative RNFL photograph severity score. RESULTS: Twenty-five (57%) subjects had thinning of the neuroretinal rim identified by evaluation of stereoscopic optic disc photographs. Despite overlap, HRT measurements of rim volume, rim area, and rim/disc ratio were significantly smaller in eyes with evidence of rim thinning than in eyes with no evidence of rim thinning. Moderate to severe RNFL damage was detected by evaluation of photographs in 25 (57%) of subjects. NFA RNFL thickness measures were smaller in eyes with moderate to severe RNFL damage than in relatively healthy eyes. CONCLUSIONS: Previous studies have documented the reproducibility of these instruments and suggested analytic techniques for improving their ability to differentiate between normal and glaucoma eyes. Our results indicate that despite overlap in values, these instruments provide measurements that reflect clinically relevant features of the optic disc and RNFL. Whether these technologies can improve our ability to detect glaucomatous progression over time needs to be determined with well-designed longitudinal studies and comparison with established diagnostic techniques for evaluating glaucomatous optic neuropathy.

Aged↗
PubMed1999

Perineal hernia with bladder retroflexion in a female cocker spaniel.

Perineal herniation in the bitch is rare and its complication by bladder retroflexion in the bitch has not been previously reported in the literature. This case report describes a multigravid, five-year-old female cocker spaniel with bilateral perineal hernias, complicated by marked rectal sacculation and ventral bladder retroflexion. The case was managed initially by cystopexy and colopexy, followed seven days later by bilateral perineal herniorrhaphy. There was no recurrence of the problem by 12 months postsurgery.

Animals↗
PubMed1999

Ferritin mutants of Escherichia coli are iron deficient and growth impaired, and fur mutants are iron deficient.

Escherichia coli contains at least two iron storage proteins, a ferritin (FtnA) and a bacterioferritin (Bfr). To investigate their specific functions, the corresponding genes (ftnA and bfr) were inactivated by replacing the chromosomal ftnA and bfr genes with disrupted derivatives containing antibiotic resistance cassettes in place of internal segments of the corresponding coding regions. Single mutants (ftnA::spc and bfr::kan) and a double mutant (ftnA::spc bfr::kan) were generated and confirmed by Western and Southern blot analyses. The iron contents of the parental strain (W3110) and the bfr mutant increased by 1.5- to 2-fold during the transition from logarithmic to stationary phase in iron-rich media, whereas the iron contents of the ftnA and ftnA bfr mutants remained unchanged. The ftnA and ftnA bfr mutants were growth impaired in iron-deficient media, but this was apparent only after the mutant and parental strains had been precultured in iron-rich media. Surprisingly, ferric iron uptake regulation (fur) mutants also had very low iron contents (2.5-fold less iron than Fur+ strains) despite constitutive expression of the iron acquisition systems. The iron deficiencies of the ftnA and fur mutants were confirmed by Mössbauer spectroscopy, which further showed that the low iron contents of ftnA mutants are due to a lack of magnetically ordered ferric iron clusters likely to correspond to FtnA iron cores. In combination with the fur mutation, ftnA and bfr mutations produced an enhanced sensitivity to hydroperoxides, presumably due to an increase in production of "reactive ferrous iron." It is concluded that FtnA acts as an iron store accommodating up to 50% of the cellular iron during postexponential growth in iron-rich media and providing a source of iron that partially compensates for iron deficiency during iron-restricted growth. In addition to repressing the iron acquisition systems, Fur appears to regulate the demand for iron, probably by controlling the expression of iron-containing proteins. The role of Bfr remains unclear.

Aerobiosis↗
PubMed1999

Genitourinary dysplasia in a cat.

A six-month-old kitten had congenital urethral sphincter mechanism incompetence due to urethral hypoplasia and associated uterine hypoplasia and vaginal aplasia. Diagnosis was based on radiographic examination, surgical exploration and histological examination of the lower urinary tract. Surgical correction resulted in a marked clinical improvement. The cat became fully continent following treatment with phenylpropanolamine.

Animals↗
PubMed1999

Effects of extreme heat on teeth with implications for histologic processing.

This pilot study examined teeth subjected to extreme heat under laboratory conditions, and the subsequent effect of decalcification and histologic processing. Physical and microscopic findings were evaluated in relation to temperature and duration of thermal insult. Microscopic examination following decalcification and histologic processing revealed changes including severe tissue fragmentation, vapor bubbles within dentinal tubules, altered histologic staining, charring and tissue shrinkage. Dentin appeared to be the most reliable microscopic identifier of incinerated dental tissues. Temperatures above 600 degrees C strongly predicted tooth disintegration following decalcification. This finding has implications in incineration cases where histologic evidence must be maintained and examined intact.

Dental Cementum↗
PubMed1999

Spatial relationship of motion automated perimetry and optic disc topography in patients with glaucomatous optic neuropathy.

PURPOSE: To compare the spatial relationship of focal motion automated perimetry (MAP) visual field defect with focal defect in optic disc topography. METHODS: Patients (n = 12) with focal MAP visual field loss and focal change in optic disc topography were studied. The MAP visual field was divided into 12 field zones representing retinal nerve fiber layer arcuate bundles. Zones of MAP loss were related to rim area ratio (RAR), which was obtained by dividing the rim area, measured by the Heidelberg Retina Tomograph (HRT; Heidelberg Engineering, Heidelberg, Germany), into 36 10 degrees sectors and then dividing the area of each sector by the total rim area for each subject. Rim area ratio was compared to a normative database (n = 76) to quantify change in optic disc topography. In these same patients, the spatial relationship between standard automated perimetry (SAP) and short-wavelength perimetry (SWAP) and optic disc topography was also assessed. RESULTS: Motion automated perimetry superior visual field zones 14 through 19 were most often associated with a reduction in RAR for inferior sectors 24 through 29, and inferior visual field zones 4 through 7 were most often associated with a reduction in RAR for superior temporal sectors 11 through 16. Similar spatial relationships were found between SWAP and SAP and the RAR. CONCLUSION: Focal MAP visual field loss and focal changes in optic disc topography are spatially related. This relationship is similar to that found between SWAP and SAP with optic disc topography. Focal thinning or notching detected by RAR analysis might be independent of the specific functional test employed.

Glaucoma, Open-Angle↗
PubMed1998

Biphasic changes in the levels of N-methyl-D-aspartate receptor-2 subunits correlate with the induction and persistence of long-term potentiation.

N-Methyl-D-aspartate glutamate receptors (NMDAR) form ion channels made up of polypeptides from two classes of subunits; NR1 is obligatory for function whereas members of the NR2 class regulate the properties of the channel. Long-term potentiation (LTP) of synaptic transmission is an event largely dependent on NMDAR activation, and is studied as the primary cellular model of memory in the mammalian brain. While there has been a focus on non-NMDARs in mediating the expression of LTP, we report here biochemical evidence for plasticity of the NMDAR that is associated with LTP persistence in awake animals. Following the establishment of LTP in perforant path synapses of the dentate gyrus, we observed a rise in NR2B protein levels 48 h post-tetanus which was dependent upon activation of NMDARs during the tetanization, and which strongly correlated with the degree of LTP measured at this time-point. We also observed a transient increase in both NR2B and NR2A protein levels 20 min post-tetanus that returned to control levels by 4 h. These early increases were not observed in anaesthetized animals which do not sustain persistent LTP. Our data demonstrate a marked plasticity of NMDAR subunit expression, which may affect LTP persistence, as well as the subsequent ability to induce LTP at previously activated synapses.

Animals↗
PubMed1998

Synaptic activity-dependent modulation of mitochondrial gene expression in the rat hippocampus.

In order to identify genes that may underlie the maintenance of long-term potentiation (LTP) at perforant path synapses, complementary DNA libraries were synthesised from dentate gyrus total RNA extracts prepared 48 h after the induction of LTP and from control dentate gyrus extracts. Through differential screening of the LTP library we have identified the mitochondrial 12S rRNA (mt12SrRNA) as a transcript that was elevated at this late time. Northern blot analyses showed that the elevation in mt12SrRNA expression began around 8 h and persisted for at least 2 weeks post-tetanus. We then examined the expression patterns of other mitochondrially-encoded genes and demonstrated a similar elevation in their expression. mt12SrRNA levels were also elevated in other hippocampal regions, including areas CA3 and CA1 and were elevated following low-frequency stimulation or in the presence of an N-methyl-D-aspartate receptor antagonist where induction of LTP was precluded. Taken together, these observations suggest that a long-lasting up-regulation of energy production may be triggered by synaptic activity and this activity need not be of sufficient strength to induce LTP, but may be related to the induction of a metaplastic state.

Animals↗
PubMed1998

A new culture system to study the metabolism of the intervertebral disc in vitro.

STUDY DESIGN: This study determined whether entrapment of a rabbit intervertebral disc in alginate gel helped to promote the retention of normal metabolic activities by the nucleus pulposus and anulus fibrosus in tissue culture. OBJECTIVES: To establish an in vitro culture system to study the metabolism of the intervertebral disc as a whole integral organ. SUMMARY OF BACKGROUND DATA: In vitro studies of the metabolism of intervertebral discs have been scarce because of the difficulties involved in maintaining the integrity of the tissues, especially that of the nucleus pulposus, in culture medium. METHODS: Rabbit intervertebral discs were embedded in alginate gel and maintained in culture for as long as 1 month. At weekly intervals, experiments were performed to measure the rate of proteoglycan synthesis and to characterize proteoglycans newly synthesized by cells in the anulus fibrosus and nucleus pulposus. In addition, at these same time intervals, the contents of sulfated proteoglycans, antigenic keratan sulfate, hyaluronan, and collagen in these two intervertebral disc tissues were measured to evaluate tissue integrity. Intervertebral discs cultured in medium alone were used as controls and analyzed in parallel. RESULTS: The anulus fibrosus and nucleus pulposus of intervertebral discs cultured in alginate gel sustained a higher rate of proteoglycan synthesis and maintained a higher content of extracellular matrix components than the respective controls at all times. CONCLUSIONS: This new alginate tissue culture system should prove useful for studying the metabolism of whole intervertebral discs.

Alginates↗
PubMed1998

Screening of myopic photorefractive keratectomy in eye bank eyes by computerized videokeratography.

BACKGROUND: In contrast to incisional keratotomy, corneas that have undergone photorefractive keratectomy may be difficult to detect by inspection with slitlamp biomicroscopy alone. Eye bank corneas that have undergone high myopic refractive surgical correction could potentially result in substantial postoperative hyperopic correction if used as donor tissue for corneal transplantation. Surface irregularities or displacement of the treated optical zone within the graft in relation to the entrance pupil of the recipient could result in significant induced astigmatism and distortion. This study examines computerized videokeratographic screening of eye bank globes as a strategy for detecting myopic photorefractive keratectomy. METHODS: Preoperative and postoperative corneal topographic maps of freshly enucleated human and rabbit eyes that have undergone myopic photorefractive keratectomy with an excimer laser were placed in a globe-fixating device and analyzed using a vertically oriented videokeratoscope. The same system was applied in an actual eye bank setting, and potentially transplantable globes from donors without a history of corneal surgery were analyzed. RESULTS: Computerized videokeratography using a vertically mounted system reliably detected photorefractive keratectomy in 12 of 12 human eye bank corneas treated by excimer photorefractive keratectomy in a range between -1.5 to -6.0 diopters. This method also detected similar changes on lased rabbit corneas enucleated 6 weeks after excimer surgery. Data processed with the tangential mode yielded a "bull's-eye" topography pattern reflecting central corneal flattening that was more sensitive in detecting myopic corrections than the conventional axial formula-based color maps. False-positive results were not detected in 96 cadaver globes sequentially screened in the eye bank. CONCLUSIONS: Computerized videokeratography represents a feasible method to screen donor globes for myopic photorefractive keratectomy as shown by the in vitro and rabbit models. However, only whole globes and not corneoscleral sections are amenable to processing with this technique. Tangential maps provided greater sensitivity in detecting low myopic corrections than the axial formula-based color maps.

Animals↗