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Biomedical subjects

D W Williams

Publications and source records attributed to D W Williams.

At least 19 recordsLinked to original sources

Identification of Candida species by PCR and restriction fragment length polymorphism analysis of intergenic spacer regions of ribosomal DNA.

The PCR was used to amplify a targeted region of the ribosomal DNA from 84 Candida isolates. Unique product sizes were obtained for Candida guilliermondii, Candida (Torulopsis) glabrata, and Candida pseudotropicalis. Isolates of Candida albicans, Candida tropicalis, Candida stellatoidea, Candida parapsilosis, and Candida krusei could be identified following restriction digestion of the PCR products.

Base Sequence

Positron emission tomography in the evaluation of laryngeal carcinoma.

Positron emission tomography (PET) is a relatively new radiologic imaging technique based on glucose analog uptake and metabolism in tumor tissue. In this study, PET was used in evaluating 38 patients with laryngeal cancer. Twenty-five patients were examined with PET prior to treatment to study the reliability of PET in identifying the primary tumor and assessing regional nodal status; 13 patients who had previously received irradiation with curative intent and who represented differential diagnostic problems were imaged to differentiate between irradiation effects and recurrent or residual cancer. Findings for both groups were compared to results of clinical evaluation and those of computed tomography (CT) and magnetic resonance imaging (MRI). The PET results were essentially identical to those of CT, MRI, and clinical evaluation in identifying metastatic lesions (82% correct), and were as reliable as CT and MRI for correctly identifying primary tumors (88%). Positron emission tomography was most helpful in differentiating recurrent tumor from postirradiation tissue sequelae. However, its lack of anatomic detail made PET less valuable for primary staging and therapeutic planning. It may enhance the diagnostic accuracy of CT and MRI where anatomic distortions occur or where diagnostic criteria for CT and MRI are ambiguous.

Carcinoma

A comparative diagnostic study of head and neck nodal metastases using positron emission tomography.

A prospective study was conducted to compare the accuracy of clinical examination, computed tomography (CT), and positron emission tomography (PET) in identifying head and neck squamous cell carcinoma metastatic to cervical lymph nodes. The findings in the necks of 49 patients evaluated by clinical examination and CT were compared to the findings in the same necks by PET, a newly available metabolic imaging modality. Pathology specimens were available for 45 of the necks. The findings of PET and CT correlated in 84% of cases. In the cases that did not correlate, CT proved correct in four of five cases. PET (82%) and CT (84%) were comparable and were both better than clinical examination (71%) in correctly identifying the presence or absence of metastatic disease.

Carcinoma, Squamous Cell

Preoperative identification of benign versus malignant parotid masses: a comparative study including positron emission tomography.

Various diagnostic tools were used in 26 patients with parotid masses to determine their value in preoperative malignant or benign categorization. These tools were positron emission tomography (PET), clinical examination, fine-needle aspiration biopsy (FNAB), computed tomography (CT), and magnetic resonance imaging (MRI). PET identified all 26 lesions and all 12 malignant lesions, but made the correct categorization in only 69% of cases. Thus, it was not as good as the more conventional diagnostic methods, their correct categorizations being 85% (clinical), 87% (CT/MRI), and 78% (FNAB) in the same patients.

Biopsy, Needle

SIMUL: an accurate method for the determination of receptor subtype proportions using a personal computer.

Many tissues possess two classes of binding sites for a drug. To estimate the proportions of each it is necessary either to use selective ligands or to perform competition experiments in which the binding of a radioligand is inhibited by a selective unlabeled ligand. However, this method will only be accurate provided the radioligand is non-selective. A selectivity of 2- to 3-fold for one receptor may produce errors of 50% or more in the estimates, depending on the concentration of radioligand chosen. Since most ligands are selective to some extent simple estimates will often provide inaccurate information. The computer program described here (SIMUL) determines the proportions of receptor subtypes by considering the relative affinities of the competing agent for the receptor subtypes, the selectivity of the radioligand and their associated concentrations.

Animals

Effects of prolonged infusion of dopexamine on beta 1- and beta 2-adrenoceptors in guinea-pig myocardium.

1. The effects of 7-day infusion of dopexamine (50 and 200 micrograms kg-1h-1) were examined on beta 1- and beta 2-adrenoceptors in guinea-pig left ventricular membranes. 2. Receptor binding performed using the high affinity radioligand (-)-[125I]-cyanopindolol (CYP) and the beta 1-adrenoceptor antagonist CGP 20712A showed that treatment with dopexamine 200 micrograms kg-1h-1 caused a 45% reduction in beta 2-adrenoceptors and a small but not significant increase in beta 1-adrenoceptors. 3. Functional effects of dopexamine were examined in the guinea-pig isolated electrically driven left atria and K(+)-depolarized uterus. Dopexamine was an antagonist at beta 1-adrenoceptors in left atria (pKB = 4.49), and a partial agonist at beta 2-adrenoceptors in the uterus (alpha = 0.78, pD2 = 6.59). 4. The effects of dopexamine on beta 1- and beta 2-adrenoceptor density in guinea-pig ventricular myocardial membranes may be related to agonist activity at beta 2-adrenoceptors and antagonist activity at beta 1-adrenoceptors.

Adrenergic beta-Agonists

Pituitary gland: MR imaging of physiologic hypertrophy in adolescence.

The size and shape of pituitary glands in 169 children, adolescents, and young adults were analyzed with T1-weighted sagittal magnetic resonance (MR) images. In patients younger than 12 years old, no pituitary gland was found to be more than 6 mm in height. In adolescents, definite evidence for physiologic (pubertal) pituitary hypertrophy was seen in both sexes, although it was much more prominent in girls. The pituitary glands of four of 32 teenage girls measured 8-10 mm, but no teenage boy had a gland taller than 7 mm. Young adults aged 21-30 years had significantly (P less than .05) smaller glands than teenagers of the same sex. Significant (P = .0001) variations in the shape of the pituitary glands according to patient age and sex were also noted. Convex upper margins were seen in 56% of teenage girls, while this shape was noted in only 18% of the remaining patients of either sex. In eight of 32 teenage girls (25%) the pituitary glands were nearly spherical on sagittal images; this shape was not recorded in any other group. The normal maturation sequence of the pituitary gland apparently involves a period of physiologic hypertrophy in teenagers. This is manifest in girls by a significant change in both pituitary size and shape, while the glands of boys undergo a transformation in size only.

Adolescent

Direction perception in complex dynamic displays: the integration of direction information.

We created random-dot cinematograms in which each dot's successive movements were independently drawn from a Gaussian distribution of directions of some characteristic bandwidth. Such a display, comprising many different, spatially intermingled local motion vectors, can produce a percept of global coherent motion in a single direction. Using pairs of cinematograms, direction discrimination of global motion was measured under various conditions of direction distribution bandwidth, exposure duration, and constancy of each dot's path. A line-element model gave an excellent account of the results: (i) over a considerable range, discrimination was unaffected by the cinematogram's direction distribution bandwidth; (ii) only for the briefest presentations did changes in duration have an effect; (iii) so long as the overall directional content of the cinematogram remained unchanged, the constancy or randomness of individual dots' paths did not affect discrimination. Finally, the line-element model continued to give a good account of the results when we made additional measurements with uniform rather than Gaussian distributions of directions.

Discrimination, Psychological

Evidence for autocrine production of IGF-1 in human thyroid adenomas.

We have recently shown that epithelial cells from a high proportion of benign human thyroid tumours (follicular adenomas) have escaped from the requirement of the normal cell for an exogenous source of insulin-like growth factor 1 (IGF-1), suggesting either autocrine production or intracellular generation of an IGF-1-induced growth signal. We show here that conditioned medium from these adenoma cells can confer IGF-1 independence on normal thyroid epithelial cells and that this activity is abolished by immunoadsorption with an anti-IGF-1 antibody. In addition, tumour but not normal cells contain immunoreactive IGF-1. Our data provide the first evidence for autocrine production of IGF-1 (or a related factor) in a benign epithelial tumour and suggest that this may be a key early step in thyroid tumorigenesis.

Adenoma

Orthodontics.

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Education, Dental, Graduate

Loss of dependence on IGF-1 for proliferation of human thyroid adenoma cells.

The proliferative responses to IGF-1 (Somatomedin C) and TSH, as assessed by 3H-thymidine (3H-TdR) incorporation and autoradiographic labelling index (LI), of suspension and monolayer cultures of human thyroid follicular epithelium derived from both normal and adenoma tissue have been compared. In cultures of normal follicles, whilst neither TSH nor IGF-1 alone produced any effect, a combination of TSH (0.1 mU ml-1) together with IGF-1 (10 ng ml-1) induced a highly significant proliferative response as shown by a peak of 3HTdR incorporation and LI, 4-5 days after growth factor addition. The TSH concentration-effect curve was bell-shaped, a higher concentration of TSH (10 mU ml-1) resulting in a reduced response. In cultures derived from adenoma tissue, however, TSH alone at 0.1 mU ml-1 was sufficient to permit a highly significant proliferative response (equivalent to, or greater than the normal) in 4 out of 5 adenomas examined; again a higher concentration of TSH (10 mU ml-1) resulted in a diminished response. Addition of IGF-1 (10 ng ml-1) produced no significant change in the response to TSH (0.1 mU ml-1) in 3 of these 4 adenomas, and significantly inhibited the response in the fourth adenoma. It is concluded that escape from the requirement for an exogenous source of IGF-1 may be a key step in the development of human thyroid epithelial (follicular cell) neoplasia.

Adenoma

Ventilator-induced pulmonary pseudocysts in preterm neonates.

Twenty-three pulmonary pseudocysts were identified in 20 preterm neonates undergoing mechanically assisted ventilation. Most of the pseudocysts occurred in a right parahilar location; cysts were either single (13) or multiple/multilocular (10). The pseudocysts persisted from less than 2 days to longer than 3 months (modal duration, 7 days), and they were commonly associated with generalized pulmonary interstitial emphysema (18 of 20), pneumothorax (18 of 20), bronchopulmonary dysplasia (16 of 20), and pneumomediastinum (six of 20). The reason for the predominantly right parahilar location of these pseudocysts remains uncertain. Pulmonary pseudocysts are almost always right-sided and are associated with pulmonary interstitial emphysema and pneumothoraces; complete resolution usually occurs.

Cysts

Control of human thyroid follicular cell proliferation in suspension and monolayer culture.

We have used both suspension and monolayer cultures to investigate the in vitro control of normal human thyroid follicular cell proliferation as assessed by both [3H]TdR incorporation and autoradiography. In suspension cultures, whilst TSH alone produced no effect, inclusion of two permissive factors, namely a supraphysiological concentration of insulin (80 micrograms/ml) and a low concentration of FCS (1%) (which, in the absence of TSH, gave only a weak proliferative response) permitted a highly significant response to TSH at 0.1 mU/ml. A higher concentration of TSH (10 mU/ml) resulted in a reduced response. In monolayer cultures in contrast, insulin and FCS were themselves highly growth stimulatory, with no super-added effect on addition of TSH. Our data indicate that suspension culture provides a more valid in vitro model for the investigation of growth factor control of normal and neoplastic human thyroid epithelium.

Cell Division

Incidence of familial hypercholesterolaemia in premature deaths due to coronary heart disease.

Cholesterol estimations were performed on blood collected postmortem from a group of subjects coming to autopsy and showing that they had had a high risk for hypercholesterolaemia, and from an unselected group of subjects dying in hospital. Subjects from the first group had apparently been healthy, aged less than 45 years, had had no known risk factors for hyperlipidaemia, and showed extensive coronary artery atheroma (stenosis greater than 50% by diameter). Eleven cases from 485 consecutive autopsies fulfilled these criteria; three showed considerable hypercholesterolaemia (11.2, 11.8, and 21.6 mmol/L). Family studies confirmed the diagnosis of familial hypercholesterolaemia in one case; the other two remain unproven. Cholesterol measurement by cholesterol oxidase and quinoneimine dye production is subject to interference by haemolysis; provided that serum haemoglobin is less than 200 mg/dl, the cholesterol underestimate is less than 5%. The decline in serum cholesterol in the group of unselected subjects was 1.7 (0.3-4.9) mmol/L, 50.4 (28-84) h postmortem. Results are means and ranges for seven subjects. Measurement of cholesterol in serum obtained postmortem (provided that the sample is not grossly haemolysed) is a valid approximation of antemortem levels: this measurement should be made when autopsy reveals evidence of premature coronary heart disease. If hypercholesterolaemia is discovered, the diagnosis of familial hypercholesterolaemia, a common genetic disorder inherited in an autosomal dominant fashion, should be considered and appropriate family studies instituted.

Adult

Coherent global motion percepts from stochastic local motions.

A percept of global, coherent motion results when many different localized motion vectors are combined. We studied the percept with dynamic random dot kinematograms whose elements took independent, random walks of constant step size; their directions of displacement were drawn from a uniform distribution. The tendency to see global, coherent flow along the mean of the uniform distribution varied with the range of the distribution. Psychometric functions were obtained with kinematograms having various step sizes and element densities. The changes in the psychometric function with step size and density are consistent with Ullman's "minimal map theory" of motion correspondence.

Form Perception