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Biomedical subjects

C B Williams

Publications and source records attributed to C B Williams.

At least 19 recordsLinked to original sources
PubMed2006

Using simulation models to predict feed intake: phenotypic and genetic relationships between observed and predicted values in cattle.

The objectives of this study were to evaluate the accuracy of the Decision Evaluator for the Cattle Industry (DECI) and the Cornell Value Discovery System (CVDS) in predicting individual DMI and to assess the feasibility of using predicted DMI data in genetic evaluations of cattle. Observed individual animal data on the average daily DMI (OFI), ADG, and carcass measurements were obtained from postweaning records of 504 steers from 52 sires (502 with complete data). The experimental data and daily temperature and wind speed data were used as inputs to predict average daily feed DMI (kg) required (feed required; FR) for maintenance, cold stress, and ADG; maintenance and cold stress; ADG; maintenance and ADG; and maintenance alone, with CVDS (CFRmcg, CFRmc, CFRg, CFRmg, and CFRm, respectively) and DECI (DFRmcg, DFRmc, DFRg, DFRmg, and DFRm, respectively). Genetic parameters were estimated by REML using an animal model with age on test as a covariate and with genotype, age of dam, and year as fixed effects. Regression equations for observed on predicted DMI were OFI = 1.27 (SE = 0.27) + 0.83 (SE = 0.04) x CFRmcg [R2 = 0.44, residual SD (s(y.x)) = 0.669 kg/d] and OFI = 1.32 (SE = 0.22) + 0.8 (SE = 0.03) x DFRmcg (R2 = 0.53, s(y.x) = 0.612 kg/d). Heritability of OFI was 0.27 +/- 0.12, and heritabilities ranged from 0.33 +/- 0.12 to 0.41 +/- 0.13 for predicted measures of DMI. Phenotypic and genetic correlations between OFI and CFRmcg, CFRmc, CFRg, CFRmg, CFRm, DFRmcg, DFRmc, DFRg, DFRmg, and DFRm were 0.67, 0.73, 0.41, 0.63, 0.78, 0.73, 0.82, 0.45, 0.77, and 0.86 (P < 0.001 for all phenotypic correlations); and 0.95 +/- 0.07, 0.82 +/- 0.13, 0.89 +/- 0.09, 0.95 +/- 0.07, 0.91 +/- 0.09, 0.96 +/- 0.07, 0.89 +/- 0.09, 0.88 +/- 0.09, 0.96 +/- 0.06, and 0.96 +/- 0.07, respectively. Phenotypic and genetic correlations between CFRmcg and DFRmcg, CFRmc and DFRmc, CFRg and DFRg, CFRmg and DFRmg, and CFRm and DFRm were 0.98, 0.94, 0.99, 0.98, and 0.95 (P < 0.001 for all phenotypic correlations), and 0.99 +/- 0.004, 0.98 +/- 0.017, 0.99 +/- 0.004, 0.99 +/- 0.005, and 0.97 +/- 0.021, respectively. The strong genetic relationships between OFI and CFRmcg, CFRmg, DFRmcg, and DFRmg indicate that these predicted measures of DMI may be used in genetic evaluations and that DM requirements for cold stress may not be needed, thus reducing model complexity. However, high genetic correlations for final weight with OFI, CFRmcg, and DFRmcg suggest that the technology needs to be further evaluated in populations with genetic variance in feed efficiency.

Animal Feed↗
PubMed2005

Review article: Population screening for colorectal cancer.

Colorectal cancer is a common cancer and common cause of death. The mortality rate from colorectal cancer can be reduced by identification and removal of cancer precursors, adenomas, or by detection of cancer at an earlier stage. Pilot screening programmes have demonstrated decreased colorectal cancer mortality; as a result many countries are developing colorectal cancer screening programmes. The most common modalities being evaluated are faecal occult blood testing, flexible sigmoidoscopy and colonoscopy. Implementation of screening tests has been hampered by cost, invasiveness, availability of resources and patient acceptance. New technologies such at computed tomographic colonography and stool screening for molecular markers of neoplasia are in development as potential minimally invasive tools. This review considers who should be screened, which test to use and how often to screen.

Colorectal Neoplasms↗
PubMed2005

Technical note: a dynamic model to predict the composition of fat-free matter gains in cattle.

Composition of empty BW (EBW) was described in terms of ether-extractable lipid (FAT) and fat-free matter (FFM), and the terms dEBW, dFAT, and dFFM were used to represent daily gains in these components. The dFFM comprised protein, water, and ash, and a model was developed to predict the composition of dFFM. The conceptual approach used in model development was based on experimental data that showed as cattle grew from birth to maturity: 1) the water content of FFM decreased and the protein and ash content increased; 2) the protein content of FFM increased at a decreasing rate; and 3) the protein-to-ash ratio in the fat-free DM was approximately constant. These results suggest that the protein content of dFFM would be high at birth and decrease at a decreasing rate as the animal grows. The protein content of dFFM was predicted as a function of the fraction of dEBW that was dFFM, FAT content of EBW, and dFFM. A fixed protein-to-ash ratio of 4.1:1 was used to calculate the quantity of ash, and water was obtained as a residual. Growth and body composition of Hereford x Angus steers from birth to 500 kg BW were simulated with a previously published model using the experimental growth data as input, and the model under discussion was used to predict the composition of dFFM. Predicted response curves of the EBW components over the growth period were similar in shape to observed data. Predicted curvilinearity in response of protein weight against FFM weight for Hereford x Angus steers was similar to observed data. The standard error about the regression of predicted on observed protein weight was 1.87 kg, and the average bias of the model was to underpredict protein weight by 0.64%. Compared with using a constant value for the protein fraction of dFFM, the model provided more accurate predictions of dEBW in an independent evaluation data set.

Animal Nutritional Physiological Phenomena↗
PubMed2004

A prospective study of colonoscopy practice in the UK today: are we adequately prepared for national colorectal cancer screening tomorrow?

AIM: To study the availability and quality of adult and paediatric colonoscopy in three National Health Service (NHS) regions. METHOD: A prospective four month study of colonoscopies in North East Thames, West Midlands, and East Anglia. PATIENTS: Subjects undergoing colonoscopy in 68 endoscopy units. RESULTS: A total of 9223 colonoscopies were studied. The mean number of colonoscopies performed over the four month period was 142 in district general hospitals and 213 in teaching hospitals. Intravenous sedation was administered in 94.6% of procedures, but 2.2% and 11.4% of "at risk" patients did not have continuous venous access or did not receive supplemental oxygen, respectively. Caecal intubation was recorded in 76.9% of procedures but the adjusted caecal intubation rate was only 56.9%. Reasons for failing to reach the caecum included patient discomfort (34.7%), looping (29.7%), and poor bowel preparation (19.6%). A normal colonoscopy was reported in 42.1%. The most common diagnosis was polyps (22.5%) followed by diverticular disease (14.9%). Inflammatory bowel disease was recorded in 13.9% and carcinoma in 3.8%. Only half of the patients remembered being told of possible adverse events prior to the procedure. Rectal bleeding requiring admission following colonoscopy was reported in six patients. The overall perforation rate was 1:769 and colonoscopy was considered a possible factor in six deaths occurring within 30 days of the procedure. Only 17.0% of colonoscopists had received supervised training for their first 100 colonoscopies and only 39.3% had attended a training course. CONCLUSION: There is serious under provision of colonoscopy service in most NHS hospitals. Endoscopy sedation guidelines are not always adhered to and there is a wide variation in practice between units. Colonoscopy is often incomplete and does not achieve the target 90% caecal intubation rate. Serious complications of colonoscopy were comparable with previous studies. Training in colonoscopy is often inadequate and improved practice should result from better training.

Adolescent↗
PubMed2004

Cancer surveillance in longstanding ulcerative colitis: endoscopic appearances help predict cancer risk.

BACKGROUND AND AIMS: The risk of colorectal cancer is increased in ulcerative colitis (UC). Patients with UC have diverse colonoscopic appearances. Determining colonoscopic markers for cancer risk could allow patient risk stratification. PATIENTS AND METHODS: Following on from an earlier study which demonstrated a correlation between inflammation severity and neoplasia risk, a case control study was performed to look for colonoscopic markers of colorectal neoplasia risk in UC. Each patient with neoplasia detected between 1988 and 2002 was matched with two non-dysplastic colitic controls. Data were collected on post-inflammatory polyps, scarring, strictures, backwash ileitis, a shortened, tubular, or featureless colon, severe inflammation, and normal looking surveillance colonoscopies. RESULTS: Cases (n = 68) and controls (n = 136) were well matched. On univariate analysis, cases were significantly more likely to have post-inflammatory polyps (odds ratio (OR) 2.14 (95% confidence interval 1.24-3.70)), strictures (OR 4.22; 1.08-15.54), shortened colons (OR 10.0; 1.17-85.6), tubular colons (OR 2.03; 1.00-4.08), or segments of severe inflammation (OR 3.38; 1.41-10.13), and less likely to have had a macroscopically normal looking colonoscopy (OR 0.40; 0.21-0.74). After multivariate analysis, a macroscopically normal looking colonoscopy (OR 0.38; 0.19-0.73), post-inflammatory polyps (2.29; 1.28-4.11), and strictures (4.62; 1.03-20.8) remained significant. The five year risk of colorectal cancer following a normal looking colonoscopy was no different from that of matched general population controls. CONCLUSIONS: Macroscopic colonoscopic features help predict neoplasia risk in UC. Features of previous/ongoing inflammation signify an increased risk. A macroscopically normal looking colonoscopy returns the cancer risk to that of the general population: it should be possible to reduce surveillance frequency to five years in this cohort.

Adolescent↗
PubMed2003

A dynamic model of metabolizable energy utilization in growing and mature cattle. I. Metabolizable energy utilization for maintenance and support metabolism.

Models to predict heat production attributable to maintenance and support metabolism in growing and mature cattle were developed on the basis of three concepts. The first concept is that animals fed fixed amounts of the same diet achieve weight equilibrium over an extended feeding period, and that the ME consumed at weight equilibrium is the maintenance requirement. The second concept is that a part of the heat production resulting from ME consumed above the maintenance requirement is associated with an elevation of vital functions (support metabolism), and this heat production can be modeled as a function of the level of feeding. The third concept is that previous levels of nutrition affect current estimates of heat production, and that this impact can be modeled as a delayed response in heat production associated with support metabolism. Experimental data on feed consumption showed that maintenance requirements varied in simple proportion to BW, not only for different breeds of mature cattle at BW equilibrium, but also for calves and growing steers held at BW stasis. Experimental data in which different breeds of cattle achieved weight equilibrium when fed fixed amounts of a specific diet were used to estimate breed parameters associated with maintenance for 21 breeds of cattle and 15 biological types of crossbred cattle. Level of feeding was estimated as a multiple of the maintenance intake and used to model heat production associated with support metabolism. Other experimental data on growing cattle were used to estimate breed parameters for predicting heat production associated with support metabolism for 21 breeds of cattle and 15 biological types of crossbred cattle. A distributed lag function was used to model the delayed response in heat production associated with support metabolism with changes in plane of nutrition. The models were tested by simulating experimental data for three breeds of weaned steers finished on high-energy diets. Results for the total heat production associated with maintenance and support metabolism expressed on a unit BW basis showed a similar response with stage of maturity when compared with other experimental data.

Animal Feed↗
PubMed2003

A dynamic model of metabolizable energy utilization in growing and mature cattle. II. Metabolizable energy utilization for gain.

Component models were developed to predict the net efficiency of ME utilization for gain in cattle and to predict daily gain using recovered energy as the input. These models were integrated into a single model to predict daily gain from ME available for gain. One component model predicts the net efficiency of ME utilization for gain using constant partial net efficiencies of 0.2 and 0.75 for ME retention as protein and fat, respectively. This model predicts net efficiency of ME utilization for gain as a function of the ratio of the energy recovered in protein to the total energy recovered. The other component model predicts daily gain as a function of recovered energy and is represented by a system of ordinary differential equations that are numerically integrated on a daily basis. This model was developed by reformulating the equations in a published body composition model that uses daily gain to predict composition of gain since recovered energy is a function of gain and composition of gain. The equations in the two component models interact in that net efficiency is used to predict recovered energy from ME for gain, and in turn, recovered energy is used to predict gain in empty BW, which determines net efficiency through composition of gain. The numeric integration procedure provides an iterative solution for net efficiency. Simulated response of net efficiency for Hereford x Angus steers at 400 kg of empty BW decreased from 0.57 to 0.52 on diets with ME densities of 3.1 and 2.6 Mcal/kg of DM, and restricting the lower-quality diet to 75% of ad libitum intake resulted in a simulated net efficiency of 0.47. These responses in net efficiency were shown to be a result of composition of gain, with leaner gains resulting in lower net efficiencies.

Animal Feed↗
PubMed2003

A dynamic model of metabolizable energy utilization in growing and mature cattle. III. Model evaluation.

Component models of heat production identified in a proposed system of partitioning ME intake and a dynamic systems model that predicts gain in empty BW in cattle resulting from a known intake of ME were evaluated. Evaluations were done in four main areas: 1) net efficiency of ME utilization for gain, 2) relationship between recovered energy and ME intake, 3) predicting gain in empty BW from recovered energy, and 4) predicting gain in empty BW from ME intake. An analysis of published data showed that the net partial efficiencies of ME utilization for protein and fat gain were approximately 0.2 and 0.75, respectively, and that the net efficiency of ME utilization for gain could be estimated using these net partial efficiencies and the fraction of recovered energy that is contained in protein. Analyses of published sheep and cattle experimental data showed a significant linear relationship between recovered energy and ME intake, with no evidence for a nonlinear relationship. Growth and body composition of Hereford x Angus steers simulated from weaning to slaughter showed that over the finishing period, 20.8% of ME intake was recovered in gain. These results were similar to observed data and comparable to feedlot data of 26.5% for a shorter finishing period with a higher-quality diet. The component model to predict gain in empty BW from recovered energy was evaluated with growth and body composition data of five steer genotypes on two levels of nutrition. Linear regression of observed on predicted values for empty BW resulted in an intercept and slope that were not different (P < 0.05) from 0 and 1, respectively. Evaluations of the dynamic systems model to predict gain in empty BW using ME intake as the input showed close agreement between predicted and observed final empty BW for steers that were finished on high-energy diets, and the model accurately predicted growth patterns for Angus, Charolais, and Simmental reproducing females from 10 mo to 7 yr of age.

Animal Feed↗
PubMed2002

Endoscopic resection of large sessile colonic polyps by specialist and non-specialist endoscopists.

BACKGROUND: Patients with large sessile colonic polyps for which endoscopic resection might be feasible are often referred directly for operation. The aim of this study was to determine the outcome of patients with such polyps diagnosed by specialist and non-specialist colonoscopists. METHODS: Patients with large (greater than 2 cm) sessile polyps detected at colonoscopy from January 1995 to July 2000 were identified. Resection technique and clinical and endoscopic outcomes were recorded. Two of the colonoscopists (B.P.S., C.B.W.) are recognized as specialists. RESULTS: Some 130 polyps were identified, 100 detected by either of two specialist endoscopists (including 14 cancers) and 30 by 14 non-specialist endoscopists (including ten cancers). Endoscopic resection of benign polyps was attempted by experts in 80 (93 per cent) of 86 cases and by non-experts in 15 of 20 cases (P = 0.03), with successful management by endoscopy alone in 61 (76 per cent) of 80 and in six of 15 cases respectively (P = 0.01). Complications occurred following three polypectomies performed by an expert (bleeding, two; pain, one) and one by a non-expert (bleeding). The estimated end-cost of management by specialists was less than half of that by non-specialists. CONCLUSION: Endoscopic resection of large sessile colonic polyps is feasible in the majority of patients and should be considered as first-line therapy. Prompt referral to a specialist endoscopist may improve outcomes by avoiding operation or enabling complete excision at a single endoscopy session.

Adult↗
PubMed2002

Patient pain during colonoscopy: an analysis using real-time magnetic endoscope imaging.

BACKGROUND AND STUDY AIMS: Colonoscopy is generally perceived as being a painful procedure. Contributory factors are: stretching of the colonic wall and mesenteric attachments from looping of the instrument shaft, overinsufflation, the degree of torque or force applied to the colonoscope shaft, and patient pain threshold. The aim of this study was to determine the frequency of pain episodes experienced during diagnostic colonoscopy and the corresponding colonoscope configuration, utilizing real-time magnetic endoscope imaging (MEI). PATIENTS AND METHODS: Consecutive outpatients undergoing colonoscopy were studied. Patients with previous colonic resections were excluded. Procedures were commenced with antispasmodics only, and patient sedation was self-administered whenever significant discomfort was experienced, using a patient-controlled analgesia (PCA) syringe pump. All "demands" were correlated with the MEI record, which was subsequently analysed. RESULTS: A total of 650 demands were recorded in 102 patients. Seventy-seven percent of all demands occurred with the colonoscope tip in the sigmoid colon, 7 % in the descending colon, 6 % at the splenic flexure, 5 % in the transverse colon, and 4 % in the proximal colon. Ninety percent of all pain episodes coincided with either looping (79 %) or straightening of the colonoscope shaft (11 %); presumed overinsufflation being an infrequent cause of pain (9 %). Of the loops encountered during colonoscopy, the N-sigmoid spiral loop was associated with the majority of pain episodes (56 %). Looping was both more frequent ( P = 0.0002) and less well tolerated in women than in men ( P = 0.0140). CONCLUSIONS: This study is the first to document pain at colonoscopy accurately. Looping, particularly in the variable anatomy of the sigmoid colon, is the major cause of pain, especially in women. Use of MEI may improve pain control by facilitating the straightening of loops within the sigmoid colon, and by enabling the endoscopist to target patient analgesia.

Analgesics↗
PubMed2001

Requirement for Ca2+/calmodulin-dependent kinase type IV/Gr in setting the thymocyte selection threshold.

The outcome of thymocyte selection is influenced by the nature of Ca2+ signals transduced by the TCR. Robust Ca2+ responses characterize high-affinity, negatively selecting peptide/TCR interactions, while modest responses typify lower-affinity, positively selecting interactions. To elucidate mechanisms by which thymocytes decode distinct Ca2+ signals, we examined selection events in mice lacking Ca2+/calmodulin-dependent protein kinase type IV/Gr (CaMKIV/Gr), which is enriched in thymocytes. CaMKIV/Gr-deficient thymocytes exhibited impaired positive selection and defective Ca2+-dependent gene transcription. Significantly, CaMKIV/Gr deficiency raised the selection threshold of peptide/TCR interactions such that a peptide that normally induced weak negative selection instead promoted positive selection. These results demonstrate an important role for CaMKIV/Gr in sensitizing thymocytes to selection by low-affinity peptides.

Animals↗
PubMed2001

Spatial coherence does not affect contrast discrimination for multiple Gabor stimuli.

Gestalt grouping rules imply a process or mechanism for grouping together local features of an object into a perceptual whole. Several psychophysical experiments have been interpreted as evidence for constrained interactions between nearby spatial filter elements and this has led to the hypothesis that element linking might be mediated by these interactions. A common tacit assumption is that these interactions result in response modulation which disturbs a local contrast code. We addressed this possibility by performing contrast discrimination experiments using two-dimensional arrays of multiple Gabor patches arranged either (i) vertically, (ii) in circles (coherent conditions), or (iii) randomly (incoherent condition), as well as for a single Gabor patch. In each condition, contrast increments were applied to either the entire test stimulus (experiment 1) or a single patch whose position was cued (experiment 2). In experiment 3, the texture stimuli were reduced to a single contour by displaying only the central vertical strip. Performance was better for the multiple-patch conditions than for the single-patch condition, but whether the multiple-patch stimulus was coherent or not had no systematic effect on the results in any of the experiments. We conclude that constrained local interactions do not interfere with a local contrast code for our suprathreshold stimuli, suggesting that, in general, this is not the way in which element linking is achieved. The possibility that interactions are involved in enhancing the detectability of contour elements at threshold remains unchallenged by our experiments.

Contrast Sensitivity↗
PubMed2001

Design of a multicentre randomised trial to evaluate flexible sigmoidoscopy in colorectal cancer screening.

A randomised, controlled trial in progress in 14 United Kingdom and six Italian centres is evaluating screening for colorectal cancer using a single flexible sigmoidoscopy (FS) at around the age of 60 with removal during FS of all small adenomas, and colonoscopy for "high risk" polyps. The regimen aims to ensure that 95% of people (with either no polyps or only low risk polyps) complete the entire screening process in a single visit. This paper describes the rationale and design of the trial. Participants were patients aged between 55 and 64 on the lists of designated general practitioners (GPs) who were not excluded by their GP. A two stage recruitment procedure was employed to raise compliance rates in the intervention group. Potentially eligible persons were sent an "interest in screening" questionnaire; those who responded positively were randomised to the intervention or control groups. The trial is sufficiently large to estimate within narrow confidence intervals the magnitude of benefit and the duration of effect and optimum age for a single screen. It also examines the feasibility and acceptability of the screening regimen, and will identify training and quality assurance issues. Recruitment and screening are now complete and all baseline data have been collected. The first analysis of the effect on colorectal cancer incidence and mortality rates and suitability for a national screening programme can be expected in 2004.

Age Factors↗
PubMed2001

Contour interaction for an easily resolvable stimulus.

It is well known that adjacent contours can reduce the visual acuity of single letters. Although this has traditionally been considered only in terms of a neural-based interaction, it has recently been suggested that the information content in the stimulus may account for the interaction. Here we ask the question, "Do similar interference effects occur for the discrimination of low-contrast letters whose size is larger than that corresponding to the resolution limit?" If so, previous acuity-based interaction results may be of more general importance. We show that while there are interference effects of nearby contours, they are of a form different from that observed at the resolution limit. In particular, the contrast polarity of the nearby contour is unimportant, which in turn suggests that a physical explanation is inappropriate. Also, the discrimination of an easily resolvable, unflanked Landolt C target requires information over a much wider spatial-frequency range than its counterpart at the resolution limit.

Discrimination, Psychological↗
PubMed2000

Effect of magnetic endoscope imaging on colonoscopy performance: a randomised controlled trial.

BACKGROUND: Colonoscopy can be technically challenging because of unpredictable colonoscope looping. Without imaging, straightening the colonoscope is sometimes difficult since the endoscopist has to guess where the tip is. Magnetic endoscope imaging (MEI), a new non-radiographical technique for picturing the colonoscope shaft in real time, could facilitate loop straightening and thus improve performance. METHODS: We assessed trainees and endoscopists with much experience of routine outpatient colonoscopy. In group 1, trainees examined 113 consecutive patients. MEI views were recorded in all examinations, but procedures were randomised to be done by two trainees, either with the endoscopist and endoscopy assistants viewing the imager display (n=58), or without the imager view (n=55). In group 2, two skilled endoscopists were randomised (as with group 1) to undertake consecutive examinations (n=183) either with (n=92) or without (n=91) the MEI view. MEI views of all procedures were analysed retrospectively. FINDINGS: In both groups, intubation times were shorter (median 11.8 min [4.3-31.5] vs 15.3 min [4-67] [group 1]; 8.0 min [2.6-40.8] vs 9.3 min [2.5-52.6] [group 2]) and number of attempts at straightening the colonoscope fewer (median 5 [0-20] vs 12 [0-57] [group 1]; 7 [0-55] vs 10 [0-80] [group 2]), when the endoscopist was able to see the imager view. In group 1, colonoscopy completion rates were also higher (100% [58] vs 89% [49]) and duration of looping was reduced (median 3 min [0-18.8] vs 5.4 min [0-44.5]) when the imager could be seen. Abdominal hand pressure was more effective when the endoscopist and endoscopy assistant could see the imager view. INTERPRETATION: MEI significantly improves performance of colonoscopy, particularly when used by trainees, or by experts in technically difficult cases; loops were straightened or controlled effectively, resulting in quick intubation times and high completion rates.

Adolescent↗
PubMed2000

Ligand-specific selection of MHC class II-restricted thymocytes in fetal thymic organ culture.

Positive and negative selection of thymocytes is determined by the specificity of the TCR and signaling through its associated molecules. We have studied selection of thymocytes bearing a MHC class II-restricted TCR using fetal thymic organ culture. This system allows the addition of peptides to the already diverse panoply of endogenous peptide ligands and is useful for analyzing ligand-specific negative selection of CD4 single positive (CD4SP) thymocytes. The data reveal that the ability of a given ligand to mediate negative selection is related to its dissociation rate from the TCR. We find that negative selection is very sensitive, and only the weakest ligand that we can identify fails to induce negative selection. None of the numerous peptides tested were able to induce an increase in CD4SP thymocytes. In addition, the ligands that induce negative selection of CD4SP thymocytes also cause an increase in numbers of CD8SP thymocytes bearing high levels of the class II-restricted TCR. Although these cells have a cell surface phenotype consistent with positive selection, they most likely represent cells in the process of negative selection. Further analysis reveals that these cells are not induced by these ligands in intact adult animals and that their induction is probably only revealed in the organ culture system.

Amino Acid Substitution↗