Search PubMedSearch

Biomedical subjects

J L King

Publications and source records attributed to J L King.

At least 19 recordsLinked to original sources

Computer-assisted diagnosis of breast cancer using a data-driven Bayesian belief network.

This study investigates a simple Bayesian belief network for the diagnosis of breast cancer, and specifically addresses the question of whether integrating image and non-image based features into a single network can yield better performance than hybrid combinations of independent networks. From a dataset of 419 cases, including 92 malignancies, 13 features relating to mammographic findings, physical examinations and patients' clinical histories, were extracted to build three Bayesian belief networks. The scenarios tested included a network incorporating all features and two hybrids which combined the outputs of sub-networks corresponding to the image or non-image features. Average areas (Az) under the corresponding ROC curves were used as measures of performance. The network incorporating only image based features performed better (Az =0.81) than that using nonimage features (Az = 0.71). Both hybrid classifiers yielded better performance (Az =0.85 for averaging and Az = 0.87 for logistic regression), but neither hybrid was as accurate as the network incorporating all features (Az = 0.89). This preliminary study suggests that, like human observers who concurrently consider different types of information, a single classifier that simultaneously evaluates both image and non-image information can achieve better diagnostic performance than the hybrid combinations considered here.

Adult

Mineralocorticoids and glucocorticoids cooperatively increase salt intake and angiotensin II receptor binding in rat brain.

Mineralocorticoids, such as deoxycorticosterone acetate (DOCA), and angiotensin II (AngII) act synergistically in the brain to elicit salt appetite. Glucocorticoids, such as dexamethasone (DEX), also may enhance the behavioral effects of DOCA and AngII. However, the brain regions involved in these behavioral interactions have not been elucidated. This study tested the hypothesis that DEX potentiates the effects of DOCA on AngII binding, especially at the AT1 receptor. We confirmed that DEX potentiated the effects of DOCA on salt appetite. Concomitantly, steroid-specific and region-specific changes in AT1 binding were noted. Specifically, in the hypothalamic paraventricular nucleus, treatment with DEX or DOCA + DEX increased AT1 binding. In the subfornical organ (SFO) and area postrema, there was an increase in AT1 binding when both steroids were combined, but not when given individually. However, there was no change in AT2 binding in any brain region studied and no change in AT1 or AT2 binding to either receptor subtype in the pituitary. The results indicate that DOCA and DEX may increase the sensitivity of the brain to the behavioral and physiological actions of AngII by upregulating AT1 receptors in the SFO and area postrema.

Angiotensin II

File management in a radiology department.

OBJECTIVE: The objective of this study was to assess the effectiveness of film management in a large urban teaching hospital. SUBJECTS AND METHODS: For 5 days in March 1998, individuals seeking access to imaging studies performed in the radiology department of a large urban hospital were questioned about their activities and were physically followed in an effort to characterize the efficiency and effectiveness of the department in servicing individuals not employed by the department. Activities in the department were recorded, and the times to visit completion and the failure rates were assessed. RESULTS: Of the 381 visitors to the department who were followed, 321 were hospital employees and 186 were physicians. The average total time spent in the department was 4 min, during which 2 min were spent viewing images or obtaining consultation. Physicians were in the department an average of only 7 min with 3 min for consultation and image viewing. During the 381 visits, we monitored 753 separate transactions, 693 of which were completed successfully. We found no instances in which a physician indicated that a patient's treatment would be delayed or altered because of film mismanagement and only one instance in which it was suggested that a study may have to be repeated. CONCLUSION: This study found a high level of efficiency and effectiveness in file room operations.

Filing

Analysis of angiotensin type 2 receptors in vasopressinergic neurons and pituitary in the rat.

Previous functional studies indicated that an angiotensin type 2 (AT2) receptor subtype may participate in the regulation of vasopressin release by angiotensin II (AngII). In the present study, AT2 receptor-directed antiserum immunohistochemically detected AT2 receptors within the hypothalamic paraventricular (PVN) and the supraoptic nuclei (SON) of the rat brain, more specifically, in identified vasopressinergic neurons. Considering the lack of AT2 binding in the PVN and the SON using receptor autoradiography, we tested the hypothesis that these AT2 receptors are transported to the posterior pituitary. Western blot analysis detected AT2 immunoreactivity in the posterior pituitary. However, no AT2 binding was detected in posterior pituitary membranes, and no AT2 binding was detected with quantitative receptor autoradiography in the neurohypophysis. Thus, if AT2 receptors are transported from the magnocellular vasopressin neurons to the posterior pituitary, their role in AngII regulation of vasopressin release at the neurohypophyseal terminals remains to be clarified.

Angiotensin II

Lactate production from glucose and response to insulin in perifused adipocytes from mesenteric and epididymal regions of lean and obese rats.

Lactate, an important metabolic substrate for peripheral tissues and the liver, is released in significant amounts from adipose tissue. Using a perifusion system, we measured lactate production from glucose and response to insulin in isolated mesenteric and epididymal adipocytes removed from fed or fasted male Wistar rats at two stages of growth and development: (a) lean rats (7 weeks to 9 weeks old, weighing approximately 250 g), and (b) fatter rats (6 months to 8 months old, weighing approximately 550 g). The results show that lactate production in perifused adipocytes is regulated by the prior nutritional state of the animals, by the adipose tissue region, and by the presence of insulin in the perifusate. In fat cells from lean rats, basal lactate production was significantly higher (p<0.05) in mesenteric cells when compared with epididymal cells, both in the fed state (7.8 nmo/10(7) fat cells per minute vs. 2.9 nmol/10(7) fat cells per minute) and after 2 days of fasting (13.6 nmol vs. 3.5 nmol). When the response to 1 mU/mL insulin was studied, however, the relative increase in lactate production produced by insulin was greater in the epididymal cells than in the mesenteric cells, in both the fed (194% vs. 91% over basal, respectively) and fasted (360% vs. 55% over basal, p<0.05) state. When larger epididymal adipocytes from fatter rats were compared with an equal number of smaller epididymal cells from leaner rats, the larger cells produced 4.99 nmol of lactate/10(7) fat cells per minute, whereas the smaller cells produced 2.93 nmol (p=0.08). Large fat cells showed a small and nonsignificant response to insulin in either type of cell (epididymal vs. mesenteric) or nutritional state (fed vs. fasted). This study indicates that distinct regional differences exist in lactate production and response to insulin. Mesenteric adipose tissue, which drains directly into the portal vein and provides substrates to the liver, may be an important source of lactate for the hepatic processes of gluconeogenesis and glycogenesis.

Adipocytes

Cryptic species in a "living fossil" lineage: taxonomic and phylogenetic relationships within the genus Lepidurus (Crustacea: Notostraca) in North America.

Lineages which exhibit little morphological change over geologic time are evolutionarily and ecologically interesting, but often taxonomically difficult. For some morphologically conservative groups, not only is it almost impossible to identify significant changes in fossil forms over time, but the relationships among extant populations are often poorly understood due to lack of known characters which clearly delimit species. Notostracan crustaceans are a classic example of such "living fossils." The paradoxical characteristics of long-term stasis in gross morphology and hypervariability of many individual morphological characters make notostracans an especially taxonomically challenging group. We used molecular and biochemical techniques to investigate the taxonomic and phylogenetic relationships of four nominal species within the genus Lepidurus in North America, three of which had been alternately abandoned, resurrected, or synonymized under a single, globally distributed morphospecies since their original descriptions in the 1800s. Data from a 330-bp sequence of the mitochondrial 12S rDNA gene and from nine allozyme loci consistently indicate five highly genetically divergent clades among the populations we used to represent the four nominal species. Diagnostic molecular characters, magnitudes of genetic divergence among clades, and the fact that these genetically distinct clades have broadly overlapping geographical ranges strongly suggest that the five clades are reproductively isolated species. One of the nominal species (L. couesii) is not monophyletic, but rather consists of two species which are not sister taxa. The other three nominal species (L. lemmoni, L. packardi, and L. bilobatus) are supported as valid phylogenetic species. The best current hypothesis for phylogenetic relationships among the five species is provided by a simultaneous analysis of both 12S rDNA and allozyme data, which places L. bilobatus and L. "couesii"-1 as sister taxa and L. "couesii"-2 as the most basal of all the Lepidurus species included in this study. These results point to the existence of cryptic species within the current classification scheme for Lepidurus, the need for further taxonomic work within the Notostraca in general, and the role that genetic techniques can play in clarifying the systematics of morphologically conservative groups.

Animals

Selection of subtle cases for observer-performance studies: the importance of knowing the true diagnosis.

RATIONALE AND OBJECTIVES: To assess the usefulness of classifying degree of difficulty in abnormality detection and to determine the effect of knowing the true diagnosis when selecting subtle images for observer-performance studies. MATERIALS AND METHODS: A total of 529 posteroanterior chest images that had been used in a multiabnormality, multireader observer-performance study were rated by three observers as to the difficulty of determining the presence or absence of each abnormality when the true diagnosis was known and when it was not known. Changes in image subtlety ratings were evaluated, and actual observer-performance results for the different groups of images grouped according to raters' classifications with and without availability of the true diagnosis were compared. RESULTS: The majority of negative cases (9,168 of 12,258, 74.8%) were rated as "easy" to determine. Substantial changes were made during the selection of the "subtle" case category when the truth was known compared with when the truth was not provided. These changes caused differences between typical and subtle cases in terms of observer performance. Combined ratings of case subtlety by agreement of multiple classifiers resulted in a well-ordered selection with decreasing observer performance as a function of subtlety ratings. CONCLUSION: Cases for observer-performance studies that stress the diagnostic system can be successfully selected in the multiple-disease setting by experienced readers and should be selected with the truth known to the raters. The degree of agreement by multiple raters can be used to refine subtlety ratings.

Diagnosis, Differential

Computed radiography versus screen-film mammography in detection of simulated microcalcifications: a receiver operating characteristic study based on phantom images.

RATIONALE AND OBJECTIVES: The authors compare a 43-micron computed radiographic system with a mammographic screen-film system for detection of simulated microcalcifications in an observer-performance study. MATERIALS AND METHODS: The task of detecting microcalcifications was simulated by imaging aluminum wire segments (200-500 microns in length; 100, 125, or 150 microns in diameter) that overlapped with tissue background structures produced by beef brisket. A total of 288 such simulations were generated and examined with both computed radiography and conventional screen-film mammography techniques. Computed radiography was performed with high-resolution plates, a 43-micron image reader, and a 43-micron laser film printer. Computed radiographic images were printed with simple contrast enhancement and compared with screen-film images in a receiver operating characteristic study in which experienced readers detected and scored the simulated microcalcifications. Observer performance was quantitated and compared by computing the area under the receiver operating characteristic curve. RESULTS: Although the resolution of the computed radiography system was better than that of commercial systems, it fell short of that of screen-film systems. For the 100-micron microcalcifications, the difference in the average area under the curve was not statistically significant, but it was significant for the larger simulated microcalcifications: the average area under the curve was 0.58 for computed radiography versus 0.76 for screen-film imaging for the 125-micron microcalcifications and 0.83 versus 1.00, respectively, for the 150-micron microcalcifications. CONCLUSION: Observer performance in the detection of small simulated microcalcifications (100-150 microns in diameter) is better with screen-film images than with high-resolution computed radiographic images.

Breast Diseases

Forced choice and ordinal discrete rating assessment of image quality: a comparison.

This study compared a five-category ordinal scale and a two-alternative forced-choice subjective rating of image quality preferences in a multiabnormality environment. 140 pairs of laser-printed posteroanterior (PA) chest images were evaluated twice by three radiologists who were asked to select during a side-by-side review which image in each pair was the "better" one for the determination of the presence or absence of specific abnormalities. Each pair included one image (the digitized film at 100 microns pixel resolution and laser printed onto film) and a highly compressed (approximately 60:1) and decompressed version of the digitized film that was laser printed onto film. Ratings were performed once with a five-category ordinal scale and once with a two-alternative forced-choice scale. The selection process was significantly affected by the rating scale used. The "comparable" or "equivalent for diagnosis "category was used in 88.5% of the ratings with the ordinal scale. When using the two-alternative forced-choice approach, noncompressed images were selected 66.8% of the time as being the "better" images. This resulted in a significantly lower ability to detect small differences in perceived image quality between the noncompressed and compressed images when the ordinal rating scale is used. Observer behavior can be affected by the type of question asked and the rating scale used. Observers are highly sensitive to small differences in image presentation during a side-by-side review.

Fourier Analysis

Immunological effects of an arginine side chain contaminating synthetically prepared peptides.

The side chain, 4-methoxy-2,3,6-trimethylbenzenesulphonyl (Mtr), is a protective group coupled to arginine to mask the omega-nitrogen, in order to protect the guanidino function during peptide synthesis by the 9-fluorenylmethoxycarbonyl (Fmoc) procedure (Walker, 1994). This group is removed at the completion of peptide synthesis; however, the cleavage process can be incomplete. We have found that animals injected with a mixed population of pure, i.e. unmodified, and Mtr-containing MBP peptides have an immunodominant humoral response to the Mtr-bearing peptide. This response is dependent on the characteristics of the MBP peptide involved. For two MBP peptides, the Mtr-containing peptide had increased binding to antibody over pure peptide. For two other peptides, only the Mtr-containing peptide bound antibody while the unmodified peptide did not. In a separate system involving a polyclonal response to an unrelated peptide from beta2-microglobulin (beta2 m), the dominance of the Mtr group was also evident. These results provide further evidence that a small side chain on a single amino acid in a peptide can markedly alter the immunogenicity and antigenicity of that peptide for antibody reactivity. This evidence emphasizes the need for a critical awareness of each component of peptide synthesis and its potential to alter the immunoreactivity of the final product.

Amino Acid Sequence

On the generalization of the receiver operating characteristic analysis to the population of readers and cases with the jackknife method: an assessment.

RATIONALE AND OBJECTIVES: A new methodology that analyzes receiver operating characteristic (ROC) data sets based on jackknifing and that considers both case and reader variability has been proposed. The purpose of this investigation was to compare results using this method to those using commonly reported methodology. METHODS: ROC data sets using discrete and continuous rating scales were analyzed using the proposed jackknifing method, and results were compared to analysis of the same data sets using the paired t test. RESULTS: The two methodologies did not result in the same significance levels, and in some cases, the difference was sufficient to affect conclusions regarding comparisons of diagnostic modalities. The probability value for the jackknifing procedure is based on large sample distribution theory, and its appropriateness is unknown for sample sizes used in practice. Also, the jackknifing technique was found to be sensitive to outliers resulting when data from the computer programs used to estimate area under the ROC curve failed to converge. CONCLUSION: Although the proposed methodology yields reasonable results, several fundamental and practical issues must be addressed before it can be used widely as the analytic method of choice in ROC studies comparing different imaging techniques or reading environments.

Analysis of Variance

Imaging systems evaluation: effect of subtle cases on the design and analysis of receiver operating characteristic studies.

OBJECTIVE: Large-scale receiver operating characteristic (ROC) studies are expensive and time-consuming. If most of the difference in diagnostic accuracy occurs in a subset of subtle cases, considerable effort could be saved by restricting comparisons to this subset. We investigate the effect of subtle cases on diagnostic accuracy, the magnitude of error that can occur because of an imbalance of subtle cases in two groups, and the potential for sample size reductions if only subtle cases are used. METHODS: Data from a previous study of posteroanterior chest radiographs were reanalyzed separately for subsets of typical cases and subsets of subtle cases. Actually positive and actually negative cases were classified as subtle or typical and as difficult or easy for diagnosis of the specific abnormality. The area under the ROC curve (Az) was used as the measure of diagnostic accuracy. Pairwise comparisons were done among three techniques and for the detection of nodules and interstitial disease. RESULTS: The performance index (Az) was significantly (> or = 25%) lower for the subset of subtle cases as compared with the subset of typical cases. The difference in observer performance between two techniques was more often greater in the subset of subtle cases than in the subset of typical cases. CONCLUSION: The difference in diagnostic accuracy between the subset of typical cases and the subset of subtle cases is large enough that a difference in the proportion of subtle cases in two samples could result in clinically significant false differences in observer performance. Furthermore, the generally larger difference observed in the group of subtle cases suggests that sample sizes for some experiments could be reduced by 45-90% if the experiment were restricted to subtle cases.

Humans

Diagnostic reading session: temporal patterns and case-order effects.

The authors analyzed receiver-operating-characteristic studies to determine temporal patterns and performance as a function of the elapsed time in a reading session. Nineteen radiologists each read as many as 300 chest images with use of seven different display modalities, including conventional and laser-printed film and high-resolution soft display. With a computerized reporting system, the ratio of observers' interpretation rates (time to diagnosis) were recorded for the last five and 10 compared with the first five and 10 of 30-40 cases seen in sessions lasting 45-110 minutes. Observers tended to accelerate their interpretation as the sessions progressed by an average of 15% (P < .001). The acceleration was consistent for all readers (both fast and slow) with a variety of display modes under the nonrestricted time environment.

Humans

Clinical outcome of cardiac patients with negative thallium-201 SPECT and positive rubidium-82 PET myocardial perfusion imaging.

In a previous comparison of 202 consecutive patients who underwent myocardial perfusion imaging with both 201Tl SPECT and 82Rb PET, 27 patients were identified as having true-positive 82Rb images, but false-negative 201Tl images. The purpose of this report is to determine the effect of correct image interpretation of coronary artery disease on the final management of those patients and compare it to the previous management scheme wherein a negative image was usually accepted as the end point unless clinical symptoms dictated otherwise. A follow-up study of the clinical course and outcome of these studies showed that 63% (17/27) of the patients with a true-positive 82Rb PET image were recommended for revascularization procedures. It is doubtful that this majority of patients would have received either surgical or interventional management based on the false-negative 201Tl SPECT procedure alone.

Angioplasty, Balloon, Coronary

A 3' splice site-binding sequence in the catalytic core of a group I intron.

Ribozymes use specific RNA-RNA interactions for substrate binding and active-site formation. Self-splicing group I introns have approximately 70 nucleotides constituting the core, a region containing sequences and structures indispensable for catalytic function. The catalytic core must interact with the substrates used for the two steps of the self-splicing reaction, that is, guanosine, the 5'-splice-site helix (P1) and the 3' splice site. Mutational evidence suggests that core sequences near segment J6/7 that joins the base-paired stems P6 and P7, and the bulged base of P7(5'), participate in binding guanosine substrate, but nothing is known about the interactions between the core, the 5'-splice-site helix and the 3' splice site. On the basis of comparative sequence data, it has been suggested that two specific bases in the catalytic core of group I introns might form a binding sequence for the 3' splice site. Here we present genetic evidence that such a binding site exists in the core of the Tetrahymena large subunit ribosomal RNA intron. We demonstrate that this pairing, termed P9.0, is functionally important in the exon ligation step of self-splicing, but is not itself responsible for 3'-splice-site selection.

Animals

Use of the 82Sr/82Rb generator in clinical PET studies.

The use of the 82Sr/82Rb generator in clinical positron emission tomography (PET) studies of myocardial perfusion has been described. An infusion pump is used to deliver the short-lived 82Rb from the generator to the patient. Various characteristics of the generator and the infusion system are described. The 82Rb yield was 69.8 +/- 13.3% and the 82Sr breakthrough was always less than the limit of 0.02 microCi/mCi 82Rb. The yield of 82Rb increased with the flow rate and the potency of the generator. Patients with coronary artery disease were studied for myocardial perfusion abnormalities by the 82Rb PET technique and images of excellent diagnostic quality were obtained.

Coronary Circulation