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C B Williams

Publications and source records attributed to C B Williams.

At least 37 records · Page 2Linked to original sources
PubMed2000

Role of p53 tumor suppressor gene in the toxicity of TCDD, endrin, naphthalene, and chromium (VI) in liver and brain tissues of mice.

It has been postulated that tumor suppressor genes are involved in the cascade of events leading to the toxicity of diverse xenobiotics. Therefore, we have assessed the comparative effects of 0.01, 0.10, and 0.50 median lethal doses (LD(50)) of 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD), endrin, naphthalene, and sodium dichromate (VI) [Cr(VI)] on lipid peroxidation, DNA fragmentation, and enhanced production of superoxide anion (cytochrome c reduction) in liver and brain tissues of p53-deficient and standard C57BL/6NTac mice to determine the role of p53 gene in the toxic manifestations produced by these diverse xenobiotics. In general, p53-deficient mice are more susceptible to all four xenobiotics than C57BL/6NTac mice, with dose-dependent effects being observed. Specifically, at a 0.50 LD(50) dose, naphthalene and Cr(VI) induced the greatest toxicity in the liver tissue of mice, and naphthalene and endrin exhibited the greatest effect in the brain tissue. At this dose, TCDD, endrin, naphthalene, and Cr(VI) induced 2.3- to 3.7-fold higher increases in hepatic lipid peroxidation and 1.8- to 3.0-fold higher increases in brain lipid peroxidation in p53-deficient mice than in C57BL/6NTac mice. At a 0. 10 LD(50) dose, TCDD, endrin, naphthalene, and Cr(VI) induced 1.3- to 1.8-fold higher increases in hepatic lipid peroxidation and 1.4- to 1.9-fold higher increases in brain lipid peroxidation in p53-deficient mice than in C57BL/6NTac mice. Similar results were observed with respect to DNA fragmentation and cytochrome c reduction (superoxide anion production). For example, at the 0.10 LD(50) dose, the four xenobiotics induced increases of 1.6- to 3. 0-fold and 1.5- to 2.1-fold in brain and liver DNA fragmentation, respectively, and increases of 1.5- to 2.3-fold and 1.4- to 2.5-fold in brain and liver cytochrome c reduction (superoxide anion production), respectively, in p53-deficient mice compared with control C57BL/6NTac mice. These results suggest that the p53 tumor suppressor gene may play a role in the toxicity of structurally diverse xenobiotics.

Animals↗
PubMed2000

Endoscopic management of polypoid early colon cancer.

Endoscopic management of polypoid early colonic cancer (malignant polyps and polypoid carcinomas) is no longer controversial. When the endoscopist is satisfied that excision is complete and histology is "favorable" (a resection margin of 2 mm and well or moderately well differentiated tumor), surgery is unnecessary. When histology show "unfavorable" characteristics (which a few histologists still take to include invasion into lymphatics), surgical or laparoscopic resection may be indicated, providing the patient is considered at suitable risk. Surgery kills some patients without finding residual cancer and cannot save others with metastases, so it should be recommended only with due clinical consideration. Sessile or broad-based polyps, especially those in the rectum, are more likely to be "high risk" and merit specialist management if local removal is to be attempted and to allow proper histologic assessment. Endoscopic approaches such as saline injection polypectomy, india-ink tattooing, and use of the argon beam coagulator are applicable in some cases. New approaches that still require trials include ultrasonographic probes, which occasionally clarify the degree of invasion, and prototype stapling devices to allow full-thickness histologic specimens to be obtained.

Colonic Polyps↗
PubMed2000

Probability summation for multiple patches of luminance modulation.

When components of a compound pattern stimulate different visual mechanisms, psychophysical performance typically improves by a small amount consistent with probability summation amongst independent detectors. Here we extend previous summation experiments by (i) plotting full psychometric functions; and (ii) using compound stimuli with components that varied in up to three stimulus dimensions: spatial frequency (1, 4, 5 or 11 c/deg), orientation (0 degrees, +/-45 degrees ), and position. Stimulus components were isolated circular sine-phase patches of grating centred on up to four corners of an imaginary square surrounding a fixation-point. Combinations of component patches produced compound stimuli made from up to 16 components that differed in various combinations of the three stimulus dimensions. Other than when the spatial frequency was 11 c/deg, results were well described using: (i) probabilistic summation of individual psychometric functions; (ii) the Quick pooling formula; and (iii) the signal detection analysis for 2IFC developed by Tyler and Chen (2000) [Signal detection theory in the 2AFC paradigm: attention, channel uncertainty and probability summation (under review)]. We conclude that in general, nonlinear spatial summation is consistent with probabilistic summation across independent detecting mechanisms that vary in spatial frequency (a range of at least 1-5 c/deg), orientation (a range of 90 degrees ) and position (a range of at least 24 cycles at 4 c/deg). In further experiments, results were found to be consistent with probability summation for pairs of orthogonally oriented step-edge stimuli and a matrix of randomly oriented 11 c/deg sine-wave patches. This casts doubt on the generality of a recent suggestion that local interactions between colinearly oriented detectors within a spatial neighbourhood of around four cycles may contribute to nonlinear spatial summation [Bonneh & Sagi, 1998; Vision Research, 38, 3541-3553].

Contrast Sensitivity↗
PubMed2000

Development of colonoscopy teaching simulation.

After 17 years of prototyping, a first release version of the St Mark's Hospital teaching simulator is in final preparation. Advances in computer processing power and graphics cards make it possible to achieve real-time processing of colon and endoscope characteristics and a simulated endoscopic view at an acceptable cost. Realistic feel or "force feedback" for all instrument controls and shaft movements is incorporated. To make the simulator more than a "video game", a package of teaching and assessment features is to be incorporated, including interactive animated graphics to explain particular endoscope loops and situations and the variations of colonic anatomy that are typically encountered. Simulation should spare patients from being used for the early phases of training and should speed up and quantify the learning process. Simulators may introduce even experienced endoscopists to some of the advanced options available in current or future endoscopes or accessories, as well as the use of imminent new technology such as the magnetic imaging system.

Colonoscopy↗
PubMed2000

Magnetic imaging of colonoscopy: an audit of looping, accuracy and ancillary maneuvers.

BACKGROUND: Colonoscopy is one of the most frequently performed outpatient examinations. However, the procedure is still technically challenging, largely due to unpredictable looping during insertion. The aims of this study were (1) to assess the frequency of loop formation and types of loop during colonoscopy, (2) to determine the accuracy of the endoscopist's assessment of the anatomic location of the endoscope tip and of the presence and type of endoscope loop formation, and (3) to determine the efficacy of abdominal compression and change in patient position in promoting colonoscope advancement. METHODS: Consecutive patients undergoing routine, day-case colonoscopy were studied using real-time, three-dimensional magnetic endoscope imaging. All examinations were performed by expert colonoscopists, blinded to the imager view. The endoscopist estimated the position of the colonoscope tip, assessed when and what type of loop had formed, and the efficacy of ancillary maneuvers such as hand pressure or patient position change. The magnetic imager view of each procedure was recorded and retrospectively analyzed. RESULTS: One hundred complete colonoscopies were performed. Looping occurred in 91% with N-sigmoid (79%) and deep transverse (34%) being most common. Most loops (69%) were incorrectly diagnosed by the endoscopist. Atypical loops were more common in women than men (p = 0.025). The endoscopist's assessment of tip location was correct 85% of the time overall, but 100% in the cecum. Abdominal pressure was less effective (54 of 145 times, 37%) than patient position change (95 of 144 times, 66%) in promoting endoscope tip advancement. CONCLUSIONS: Looping occurs frequently during routine colonoscopy. Although the endoscopist's assessment of tip location is fairly accurate, the majority of colonoscope loops are incorrectly appreciated. Although used frequently, ancillary maneuvers (abdominal compression and patient position change) are effective in only 52% of attempts.

Adolescent↗
PubMed2000

A new variable stiffness colonoscope makes colonoscopy easier: a randomised controlled trial.

BACKGROUND: Colonoscopy remains technically difficult in 10-20% of procedures due to variable colonic anatomy and fixation. The ability to vary endoscope shaft flexibility may help insertion to the caecum. METHODS: Consecutive patients attending for day case colonoscopy were randomised to examination with either the conventional Olympus CF200HL (200HL) or a new variable stiffness (VS) colonoscope. Intubation time, use of stiffening function, and patient pain scores were compared. RESULTS: Of 100 cases, 43 were performed with the 200HL and 57 with the VS. Four incomplete examinations occurred with the 200HL (two sigmoid fixations, two benign strictures) and two with the VS (one obstructing cancer, one fixed sigmoid). Changing to the paediatric scope was successful in all but one patient from each group (obstructive lesions). Stiff mode was applied 23 times in 18 patients and was effective in 15 of these. Intubation time was quicker with the VS (median 6 minutes 32 seconds) than with the 200HL (median 10 minutes 35 seconds) (p = 0.0005). Pain scores were less with the VS (median 7) than with the 200HL (median 24) (p = 0.0081). CONCLUSIONS: The variable stiffness colonoscope combines paediatric shaft characteristics with the ability to stiffen when needed. This instrument significantly reduces intubation time and patient discomfort. Further comparisons should be made with the newest colonoscopes which are less stiff.

Colonic Diseases↗
PubMed2000

Carcinoid tumour in a caecal duplication cyst.

Intestinal duplication cysts are rare congenital anomalies that may occasionally undergo neoplastic change. We report the case of a 30-year-old woman who was diagnosed to have a caecal duplication cyst. The cyst was excised and histology revealed the presence of a 10 mm diameter carcinoid tumour within the cyst wall. There was no evidence of metastatic spread and the patient remains well after 2 years follow-up. The 3 previously reported cases of carcinoid tumour arising within duplication cysts are reviewed.

Adult↗
PubMed1999

A kinetic threshold between negative and positive selection based on the longevity of the T cell receptor-ligand complex.

We have developed a unique in vivo system to determine the relationship between endogenous altered peptide ligands and the development of major histocompatibility complex class II- restricted T cells. Our studies use the 3.L2 T cell receptor (TCR) transgenic mouse, in which T cells are specific for Hb(64-76)/I-Ek and positively selected on I-Ek plus self-peptides. To this endogenous peptide repertoire, we have individually added one of six well-characterized 3.L2 ligands. This transgenic approach expands rather than constrains the repertoire of self-peptides. We find that a broad range of ligands produce negative selection of thymocytes in vivo. When compared with the in vitro TCR-ligand binding kinetics, we find that these negatively selecting ligands all have a half-life of 2 s or greater. Additionally, one of two ligands examined with no detectable binding to the 3.L2 TCR and no activity on mature 3.L2 T cells (Q72) enhances the positive selection of transgenic thymocytes in vivo. Together, these data establish a kinetic threshold between negative and positive selection based on the longevity of TCR-ligand complexes.

Amino Acid Sequence↗
PubMed1999

Cutting edge: the tyrosine phosphatase SHP-1 regulates thymocyte positive selection.

The binding kinetics of the TCR for its interacting ligand and the nature of the resulting signal transduction event determine the fate of a developing thymocyte. The intracellular tyrosine phosphatase SHP-1 is a potential regulator of the TCR signal transduction cascade and may affect thymocyte development. To assess the role of SHP-1 in thymocyte development, we generated T cell-transgenic mice that express a putative dominant negative form of SHP-1, in which a critical cysteine is mutated to serine (SHP-1 C453S). SHP-1 C453S mice that express the 3.L2 TCR transgene are increased in CD4 single positive cells in the thymus and are increased in cells that express the clonotypic TCR. These data suggest that the expression of SHP-1 C453S results in increased positive selection in 3.L2 TCR-transgenic mice and support a role for SHP-1 thymocyte development.

Animals↗
PubMed1999

Accurate PEG tube placement with magnetic positional imaging.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is a common procedure and accounts for an increasing proportion of an endoscopist's workload. Serious complications can occur from inaccurate abdominal wall puncture. Electronic three-dimensional imaging has been used to aid colonoscopy. We adapted the principles of this technique to PEG insertion in a procedure called magnetic positional imaging. METHODS: Magnetic positional imaging was used to determine the abdominal wall puncture site and angle of insertion that would provide the shortest distance from abdominal wall to the stomach. The pull-through technique was used to perform PEG. RESULTS: PEG insertion with magnetic positional imaging was performed on four patients without complications. The average distance between the internal and external sensors was 5 mm. CONCLUSION: A new technique, magnetic positional imaging, facilitates the pull-through technique for PEG. Additional studies are needed to clarify the potential benefit in endoscopic practice.

Abdominal Muscles↗
PubMed1999

The interaction of first- and second-order cues to orientation.

The visual system is sensitive to orientation information defined both by first-order (luminance) and by second-order (texture) cues. We consider how these orientation cues are computed and how they affect one another. We measured the perceived orientation of the first and second-order components of Gabor patches (the carrier and envelope, respectively) and report a dependence of the perceived orientation of each on the orientation of the other, and on the spatial frequency of the carrier. Fixing the carrier orientation near that of the envelope interferes with envelope orientation judgements. This interference is reduced by adding a small (subthreshold) rotation to the carrier indicating that the site of interference is early. When the gross relative orientation of carrier and envelope is varied, the carrier appears systematically tilted towards the envelope. However, provided envelope and carrier are separated by more than approximately 10 degrees, the perceived envelope orientation appears tilted away from the carrier. The size of these effects increases with decreasing carrier spatial frequency, and with increasing exposure duration. When the envelope and carrier are both non parallel and non-perpendicular Fourier energy is distributed asymmetrically across orientation. We demonstrate that, for a channel-based orientation code, this asymmetry induces a shift in mean orientation that is sufficient to explain illusory tilting of carriers. The illusory tilting of the envelope, as a function of carrier orientation and spatial frequency, demonstrates that human ability to demodulate contrast information is far from ideal and cannot be explained by existing two-stage filter-rectify-filter models. We propose that illusory tilting of the envelope is due to selective connectivity between first- and second-stage filters whose purpose is to dissociate the type of image structure producing each class of cue.

Cues↗
PubMed1999

The orientation discrimination deficit in strabismic amblyopia depends upon stimulus bandwidth.

We show that the previously reported orientation deficit in amblyopia (Skottun, B. C., Bradley, A., & Freeman, R. D. (1986). Orientation discrimination in amblyopia. Investigative Ophthalmology and Visual Science, 30, 532-537) also occurs for arrays of randomly positioned Gabor micropatterns for which explanations based on either neural disarray or local neural interactions would not hold. Furthermore, when using Gabors, we show that the deficit varies with the spatial frequency and orientational bandwidth of the stimuli used to measure it. We discuss two competing explanations for this, one based on a broader underlying detector bandwidth in amblyopia (both orientation and spatial frequency) and the other based on a selective deficit of first-order, as opposed to second-order orientation processing in strabismic amblyopia. Our results favour the latter interpretation.

Amblyopia↗
PubMed1999

Depth of insertion at flexible sigmoidoscopy: implications for colorectal cancer screening and instrument design.

BACKGROUND AND STUDY AIMS: The depth of insertion at flexible sigmoidoscopy is variable, depending upon bowel preparation, patient tolerance and distal colonic anatomy. Many endoscopists routinely aim to insert the 60 cm flexible sigmoidoscope to the splenic flexure; however internal endoscopic markers are unreliable, making the true anatomical extent of the examination difficult to assess. The aim of this study was to assess the depth of insertion at flexible sigmoidoscopy. PATIENTS AND METHODS: Two separate studies were done. In the first (study 1), magnetic endoscopic imaging was used to determine the final depth of insertion at non-sedated, screening flexible sigmoidoscopy. In the second (study 2), "real-time" imaging was utilized to determine sigmoid looping and the anatomical location of the endoscope tip after 60 cm of instrument had been inserted during total or limited colonoscopy. A total of 117 consecutive average-risk patients, aged 55-65 years participated in study 1, and 136 patients underwent either limited, (33) or attempted total colonoscopy (103) in study 2. RESULTS: In study 1 the median insertion distance was 52 cm, range 20-58. In 61 % of patients the imaging system showed that the descending colon had not been visualized by the end of the procedure. Failure to reach the sigmoid/descending junction occurred in 29 (24%) patients. Reasons for failure included poor tolerance of the procedure due to pain (23 patients) inadequate preparation (3 patients) and, excessive looping (3 patients). In study 2, after 60 cm of instrument had been inserted, the splenic flexure or beyond was reached in 29% and the descending colon in 9%, whilst in 62 % the endoscope tip had not passed beyond the sigmoid/descending colon junction. A sigmoid loop formed in 70% of patients, and unusual loops such as the alpha, reverse alpha and reverse sigmoid spiral loop occurred more frequently in women compared to men (P = 0.0249). In those 104 patients where the splenic flexure was reached the mean maximum length of instrument inserted prior to reaching the flexure was 75.4 cm, (SD = 21.9). CONCLUSIONS: Examination of the entire sigmoid was not achieved in approximately one-quarter of patients undergoing screening flexible sigmoidoscopy, mainly because of discomfort. The descending colon is intubated in a minority of cases (using standard instruments), even after 60 cm has been inserted. Alternative instruments with different shaft characteristics (floppy, narrow calibre, 80-100 cm in length) may be necessary to ensure deeper routine intubation in nonsedated patients.

Aged↗
PubMed1999

Effect of selective screening for gestational diabetes.

OBJECTIVE: To estimate the percentage of pregnant women who would not be screened and the percentage of women with gestational diabetes mellitus (GDM) who would possibly remain undiagnosed if the American Diabetes Association's (ADA's) new selective screening recommendations are used rather than universal screening for GDM. RESEARCH DESIGN AND METHODS: Since 1987, the University of Michigan Health System has performed universal screening for GDM. In 1997, the ADA recommended that women having all four of the following characteristics need not be screened: age < 25 years, not members of an ethnic/racial group with a high prevalence of diabetes, normal body weight, and no family history of diabetes. We studied a random sample of the 25,118 deliveries at the University of Michigan between 1987 and 1997 to determine the prevalence of these four characteristics in our obstetric population. We also studied the prevalence of these four characteristics in 200 women who were diagnosed with GDM in the Endocrine Testing Unit and delivered at the University of Michigan between 1987 and 1997. RESULTS: Approximately 10-11% of women who delivered possessed all four low-risk characteristics and would not have been screened for GDM according to the new ADA recommendations. Only 4% of women (5 of 141) with GDM who delivered and for whom data on all four characteristics were reported possessed all four low-risk characteristics and would not have been screened. CONCLUSIONS: If the new ADA selective screening recommendations are used, few women with GDM will be missed (4%) but approximately 90% of pregnant women will still need to be screened for GDM.

Adult↗
PubMed1999

Effects of sire growth potential, growing-finishing strategy, and time on feed on performance, composition, and efficiency of steers.

Beef production systems that increase use of unharvested forages and use animals with greater potential for gain affect age and size of animals placed on a finishing regimen. This experiment was conducted to evaluate effects of genetic potential for gain, age at the start of a finishing period, and time on feed on composition, quantity, and quality of beef produced and efficiency of production during finishing. Crossbred cows were bred by AI to Charolais or Line 1 Hereford bulls that represented potentially high (HG) or moderate growth (MG) rates, respectively, to produce spring- or fall-born calves. Steer calves from these matings were placed on an individually fed finishing diet at three ages (A). Spring-born steers were started at 6 or 18 mo of age (A6 and A18), and fall-born steers were started at 12 mo of age (A12). Slaughter times (T) were at 0, 90, 180, and 270 d for A6; 68, 136, and 204 d for A12; and 0, 45, 90, and 135 d for A18. Data collected on each animal included feed intake, growth, chemical composition of the complete body and carcass, and quantitative and qualitative assessment of the meat produced. Four steers of each sire group were slaughtered in each of the 11 A-T treatment groups, and the experiment was repeated for 2 yr in the A12 groups and 3 yr in the A6 and A18 groups (n = 237). Steers sired by HG bulls were larger and produced larger carcasses and more carcass protein than MG-sired steers (S, P < .05 or .01). Steers sired by MG bulls were fatter, had higher quality grades, and accumulated fat at a faster rate than HG-sired steers, and this effect was greater in older steers (G and GA, P < .05 or .01). Sire growth potential did not affect gain, intake, live weight efficiency, tenderness, or taste panel scores (P > .2). Steers sired by HG bulls were more efficient at producing carcass weight and carcass protein at A12 and A18 than were MG-sired steers. At the end of the finishing period, older (A18), HG-sired steers were too large with insufficient fat by current industry standards, and younger (A6), MG-sired steers were too small. Our conclusions are that both HG- and MG-sired steers can produce acceptable carcasses for current market standards with comparable efficiencies of live-weight gain, but the growing and finishing strategy must be adapted to the genotype.

Animal Feed↗
PubMed1999

Acute and chronic stress-induced oxidative gastrointestinal mucosal injury in rats and protection by bismuth subsalicylate.

Reactive oxygen species (ROS) are implicated in the pathogenesis of stress-induced gastrointestinal mucosal injury. In the present study, we have investigated the effects of acute and chronic stress on the enhanced production of ROS including superoxide anion [SA; as determined by cytochrome c reduction (CCR)] and hydroxyl radicals (OH), and correlated the enhanced production of these free radicals with increased lipid peroxidation, membrane microviscosity and DNA fragmentation, indices of oxidative tissue damage, in the gastric and intestinal mucosa of female Sprague-Dawley rats. Furthermore, the protective ability of bismuth subsalicylate (BSS) against the gastrointestinal mucosal injury induced by acute and chronic stress was determined. Acute stress was induced for a period of 90 min, while chronic stress was induced for 15 min/day for 15 consecutive days. Half of the animals exposed to acute stress were pretreated orally with 15 mg BSS/kg 30 min prior to the exposure to acute stress. Similarly, half of the animals exposed to water-immersion restraint chronic stress were pretreated orally with 7.5 mg BSS/kg/day for 15 consecutive days 30 min prior to the exposure to chronic stress. Acute stress produced greater injury to both gastric and intestinal mucosa as compared to chronic stress. Acute stress increased CCR and OH production by 10.0- and 14.3-fold, respectively, in the gastric mucosa, and 10.4- and 17.0-fold, respectively, in the intestinal mucosa. Pretreatment with BSS prevented the acute stress-induced increase in CCR and OH production. Acute stress increased lipid peroxidation, DNA fragmentation and membrane microviscosity by 3.6-, 4.0- and 11.6-fold, respectively, in gastric mucosa, and 4.1-, 5.0- and 16.2-fold, respectively, in intestinal mucosa. BSS decreased acute stress-induced lipid peroxidation, DNA fragmentation and membrane microviscosity by approximately 26, 35 and 30%, respectively, in gastric mucosa, and by 20, 36 and 30%, respectively, in the intestinal mucosa. Chronic stress increased CCR and OH production by 4.8- and 6.3-fold, respectively, in gastric mucosa, and 4.6- and 6.9-fold, respectively, in intestinal mucosa. Chronic stress increased lipid peroxidation and DNA fragmentation by 2.9- and 3.3-fold, respectively, in gastric mucosa, and 3.3- and 4.2-fold, respectively, in intestinal mucosa. BSS decreased chronic stress-induced lipid peroxidation, DNA fragmentation and membrane microviscosity by approximately 41, 44 and 45%, respectively, in gastric mucosa, and by 39, 52 and 51%, respectively, in the intestinal mucosa. Daily administration of BSS provided greater protection against chronic stress-induced oxidative gastrointestinal injury as compared to the acute stress. These results demonstrate that both acute and chronic stress can induce gastrointestinal mucosal injury through enhanced production of ROS, and that BSS can significantly protect against gastrointestinal mucosal injury.

Animals↗