Biomedical subjects

Richard A Watson

Publications and source records attributed to Richard A Watson.

12 recordsLinked to original sources

PubMed2007

Exploratory factor analysis: strategies used by patients to promote health.

Strategies used by patients to promote health (SUPPH) was used to measure self-care self-efficacy in patients with cancer. The objectives of this study were (1) to determine the extent to which self-efficacy theory explained the factor structure of the SUPPH and (2) to determine the relationship of demographic data with factors of the SUPPH. Subjects were diagnosed with prostate cancer (PCa) and treated with either: (a) radical prostatectomy, (b) intensity modulated radiation therapy (IMRT) + radioactive seed implantation, or (c) IMRT + high dose rate. Subjects completed a demographic questionnaire and the SUPPH. Exploratory factor analysis of the SUPPH was performed using a varimax rotation. Subjects (n = 265) were predominately white and averaged 68 years of age. The model explained 81.3% of the total sum of eigenvalues. Two factors of the SUPPH were identified: physiological efficacy information and performance efficacy information. Younger subjects who were fully employed and earning more money had significantly higher performance self-efficacy than older subjects who were working part time and earning less money. Results are congruent with Bandura's (1997) description of self-efficacy. Use of the SUPPH may facilitate research validating Bandura's (1997) assertion that an individual's self-efficacy is related to quality of life (QOL) during chronic illness. Additional research focusing on self-efficacy and PCa patients' QOL may lead to efficacy enhancing interventions that will improve QOL of patients with PCa.

Adult↗

PubMed2005

Modular interdependency in complex dynamical systems.

Herbert A. Simon's characterization of modularity in dynamical systems describes subsystems as having dynamics that are approximately independent of those of other subsystems (in the short term). This fits with the general intuition that modules must, by definition, be approximately independent. In the evolution of complex systems, such modularity may enable subsystems to be modified and adapted independently of other subsystems, whereas in a nonmodular system, modifications to one part of the system may result in deleterious side effects elsewhere in the system. But this notion of modularity and its effect on evolvability is not well quantified and is rather simplistic. In particular, modularity need not imply that intermodule dependences are weak or unimportant. In dynamical systems this is acknowledged by Simon's suggestion that, in the long term, the dynamical behaviors of subsystems do interact with one another, albeit in an "aggregate" manner--but this kind of intermodule interaction is omitted in models of modularity for evolvability. In this brief discussion we seek to unify notions of modularity in dynamical systems with notions of how modularity affects evolvability. This leads to a quantifiable measure of modularity and a different understanding of its effect on evolvability.

Biological Evolution↗

PubMed2005

Perspective: Sign epistasis and genetic constraint on evolutionary trajectories.

Epistasis for fitness means that the selective effect of a mutation is conditional on the genetic background in which it appears. Although epistasis is widely observed in nature, our understanding of its consequences for evolution by natural selection remains incomplete. In particular, much attention focuses only on its influence on the instantaneous rate of changes in frequency of selected alleles via epistatic contribution to the additive genetic variance for fitness. Thus, in this framework epistasis only has evolutionary importance if the interacting loci are simultaneously segregating in the population. However, the selective accessibility of mutational trajectories to high fitness genotypes may depend on the genetic background in which novel mutations appear, and this effect is independent of population polymorphism at other loci. Here we explore this second influence of epistasis on evolution by natural selection. We show that it is the consequence of a particular form of epistasis, which we designate sign epistasis. Sign epistasis means that the sign of the fitness effect of a mutation is under epistatic control; thus, such a mutation is beneficial on some genetic backgrounds and deleterious on others. Recent experimental innovations in microbial systems now permit assessment of the fitness effects of individual mutations on multiple genetic backgrounds. We review this literature and identify many examples of sign epistasis, and we suggest that the implications of these results may generalize to other organisms. These theoretical and empirical considerations imply that strong genetic constraint on the selective accessibility of trajectories to high fitness genotypes may exist and suggest specific areas of investigation for future research.

Biological Evolution↗

PubMed2005

Human Papillomavirus: Confronting the Epidemic-A Urologist's Perspective.

The human papillomavirus (HPV) has long been associated with the development of penile lesions-condyloma acuminatum and verrucous carcinoma of the penis. More recently, HPV has been implicated as an etiology of more serious neoplasias in men-penile carcinoma and other anogenital squamous-cell carcinomas. HPV is now widely recognized as responsible for more than 95% of cervical cancers in women. HPV seems to have been receiving relatively scant attention to date-from physicians in general, and particularly from urologists-as a venereal disease of significant concern. Yet HPV is recognized to be the most frequently acquired sexually transmitted viral infection worldwide. It is estimated that approximately 6 million new cases of HPV are sexually transmitted annually in the United States. Fortunately, many, if not most, of these HPV infections are transient. However, each newly acquired infection has the potential to persist as an incurable, lifelong affliction, generating a significant increase in the long-term risk of cancer for patients and their sexual partners. Many of these HPV-related cancers will not become manifest until decades later.

Journal Article↗

PubMed2004

Evaluation of the incidentally discovered adrenal mass.

The increased use of abdominal ultrasonography, computed tomography, and magnetic resonance imaging has led to the classification of adrenal lesions termed the incidentally identified adrenal mass or adrenal incidentaloma. Unlike for the large, clinically, or biochemically symptomatic adrenal mass, the evaluation of patients with small, asymptomatic, or nonfunctional adrenal lesions remains controversial. The evaluation of these adrenal incidentalomas presents a challenge to endocrinologists, radiologists, and urologic surgeons alike. A multidisciplinary approach with biochemical screening and radiologic evaluation is essential to assess the nature and function of these lesions. Furthermore, it is of great importance to identify patients who are morbidly affected by hormonal hypersecretion or malignant potential. This article describes the emerging guidelines for the evaluation of the incidental adrenal mass.

Adrenal Gland Neoplasms↗

PubMed2003

Activity of the human papillomavirus E6 PDZ-binding motif correlates with an enhanced morphological transformation of immortalized human keratinocytes.

Human papillomavirus E6 oncoproteins induce the proteasomal degradation of several multi-PDZ (PSD95/Dlg/ZO-1) domain-containing proteins such as the human homologue of Drosophila discs large. Binding to PDZ domain-containing proteins is mediated by a PDZ-binding motif contained within the C-terminus of E6. The ability of E6 proteins to induce degradation of PDZ domain-containing proteins correlates with their oncogenic potential. Here we examined the biological effect of this region of the human papillomavirus type 18 E6 oncoprotein on keratinocyte morphology. Our results show that in simian virus 40-immortalized human keratinocytes, stable expression of E6 correlated with the induction of an exaggerated mesenchymal-like morphology and actin cytoskeleton disorganization compared with parental cells. The altered phenotype was accentuated in cells expressing an E6 protein containing a mutation (Arg153Leu) within a protein kinase A recognition motif that abrogates protein kinase A's negative regulation of the activity of the PDZ-binding domain. The E6-induced changes indicated an epithelial-mesenchymal transition and were supported by the finding that E6-expressing cells contained vimentin. Changes to the epithelial phenotype of cells expressing a mutant E6 protein (Thr156Glu) that is unable to degrade discs large was significantly less marked, although they did show evidence of epithelial-mesenchymal transition. These observations imply that the activity of the E6 PDZ-binding motif contributes only to a part of the transition. Further analysis of the E6 cell lines showed a decrease in adherens junction and desmosome formation. Cells expressing a functional PDZ-binding motif showed the greatest disruption of intercellular junction formation, but this did not correlate with a decrease in total cellular levels of the individual components of adhesion junctions. This suggests that the activity of the PDZ-binding motif may have influenced either the assembly or integrity of functional adhesion complexes. An E6-mediated decrease in peripheral membrane levels of PDZ proteins like discs large could be the basis for the enhanced morphological transformation of immortalized keratinocytes.

Actins↗

PubMed2003

Improved detection of renal pathologic features on multiphasic helical CT compared with IVU in patients presenting with microscopic hematuria.

OBJECTIVES: To examine the virtues of multiphasic helical computed tomography (CT) in the diagnosis of upper urinary tract lesions refractory to identification by intravenous urography (IVU). METHODS: A total of 86 patients (59 men and 27 women), 27 to 88 years old, with microscopic hematuria and negative IVU findings were examined with multiphasic helical CT consisting of a pre-enhancement, late arterial-early cortical-medullary, nephrographic, and excretory phase helical CT of the kidneys, using 3 to 5-mm collimation and 7.5-mm/s table feed. RESULTS: The multiphasic helical CT was conclusive in 84 lesions. Twenty-five cases of early papillary and medullary necrosis, 7 of 8 inflammatory lesions, 3 caliceal diverticula, 1 lupus nephritis, 26 small calculi, 2 medullary sponge kidney, 5 vascular anomalies, and 3 infarcts presented with characteristic manifestations on CT but lacked findings on IVU. Similarly 8 of 9 small malignant neoplasms, 2 small benign neoplasms, and 2 small cysts produced no detectable findings on IVU but were readily diagnosed on helical CT. CONCLUSIONS: Characteristic findings, particularly on late arterial, early corticomedullary, parenchymal, and excretory phase helical CT make possible the diagnosis of early inflammatory disease, small masses and neoplastic lesions, and vascular abnormalities. Limited resolution (needed to identify small calculi) and the lack of ability to capture phases significantly reduce the diagnostic ability of IVU.

Adult↗

PubMed2003

"Indeterminate" cystic lesion of the kidney partially lined by small cells with clear cytoplasm--malignant or benign?

Complex renal cysts, which present radiographically as "indeterminate for malignancy" (Bosniak category III), can prove challenging both pathologically and clinically. We report a case of a renal cyst that, by standard radiographic and histologic criteria, should have been diagnosed as a malignant cystic renal cell carcinoma. However, the cytogenetic profile appeared more closely consistent with cystic renal adenoma or low-grade papillary renal cell carcinoma--tumors with limited metastatic potential. We postulate that other, similarly complex, renal cysts might also be more precisely defined by meticulous histopathologic examination, supported by cytogenetic study.

Adenocarcinoma↗

PubMed2003

A computational model of symbiotic composition in evolutionary transitions.

Several of the major transitions in evolutionary history, such as the symbiogenic origin of eukaryotes from prokaryotes, share the feature that existing entities became the components of composite entities at a higher-level of organization. This composition of pre-adapted extant entities into a new whole is a fundamentally different source of variation from the gradual accumulation of small random variations, and it has some interesting consequences for issues of evolvability. Intuitively, the pre-adaptation of sets of features in reproductively independent specialists suggests a form of 'divide and conquer' decomposition of the adaptive domain. Moreover, the compositions resulting from one level may become the components for compositions at the next level, thus scaling-up the variation mechanism. In this paper, we explore and develop these concepts using a simple abstract model of symbiotic composition to examine its impact on evolvability. To exemplify the adaptive capacity of the composition model, we employ a scale-invariant fitness landscape exhibiting significant ruggedness at all scales. Whilst innovation by mutation and by conventional evolutionary algorithms becomes increasingly more difficult as evolution continues in this landscape, innovation by composition is not impeded as it discovers and assembles component entities through successive hierarchical levels.

Adaptation, Physiological↗

PubMed2002

CT-guided biopsy of indeterminate renal cystic masses (Bosniak 3 and 2F): accuracy and impact on clinical management.

The purpose of this study was to determine ability of cyst aspiration and core biopsy to differentiate malignancies, and benign lesions needing intervention from benign complex cysts in the group of Bosniak 2F and 3 renal cysts. One hundred ninety-nine indeterminate complex renal cysts were biopsied under CT or US guidance using a coaxial system (19-G sheath, 20- or 21-G Chiba or Franseen or 18-G spring biopsy needle). Cytology, amylase, lipase, LDH, fat, protein, urea nitrogen, creatine, and culture and sensitivity were assessed in all patients, histopathology in 116, and flow cytometry in 32. In 179 patients (87.9%) a definitive diagnosis was made; in 20 the specimen was inadequate. Twenty of 28 malignancies were correctly diagnosed (sensitivity 0.71); 27 of 31 benign lesions needing intervention (sensitivity 0.87) and 128 of 140 benign complex cysts (sensitivity 0.91). All inconclusive biopsies were explored revealing six malignancies. There were four CT biopsy misdiagnoses: two renal cell carcinomas; one angiomyolipoma; and one abscess. Guided cyst puncture aspiration and core biopsy significantly altered management of Bosniak 3 and 2F renal cysts obviating surgery or invasive procedures in 70% of the patients with an affirmed diagnosis of benign complex cyst and rendering timely surgical and other interventions in the remaining patients. Long-term follow-up (mean 5.6 years) revealed no further misdiagnosis.

Adult↗

PubMed2002

Computerized tomography tailored for the assessment of microscopic hematuria.

PURPOSE: We report the results of a multicenter study of arterial, corticomedullary, nephrographic and excretory phase helical computerized tomography (CT) for detecting and characterizing abnormalities causing asymptomatic microscopic hematuria. MATERIALS AND METHODS: We evaluated 350 consecutive patients, including 216 men and 134 women 23 to 88 years old, with asymptomatic microscopic hematuria of undetermined cause at 4 medical centers. Patients with known urological pathology were excluded from study. We performed 4 helical CT sequences, including pre-enhancement phase imaging from kidney to symphysis pubis, arterial phase imaging of the kidney and lower pelvis, corticomedullary nephrographic phase imaging of the kidney and lower pelvis, and excretory phase imaging from kidney to symphysis pubis with 2 to 5 mm. collimation and 1 to 1.5 pitch. RESULTS: Of 171 proved lesions 158 were correctly diagnosed. There were 10 false-positive and 13 false-negative diagnoses, indicating 0.9239 sensitivity, 0.9441 specificity, 0.9404 positive and 0.9285 negative predictive values, (p <0.001). All cases of congenital renal lesions, calculous disease, ureteral lesion and neoplastic lesion of the bladder were correctly diagnosed, as were 40 of 41 inflammatory renal, 21 of 23 renal masses and 13 of 16 inflammatory bladder lesions. In 27 patients with renal calculi the study was limited to pre-enhancement spiral CT. CONCLUSIONS: A positive diagnosis rate of 45.1% (158 of 350 cases) for the causes of heretofore refractory cases of hematuria with high sensitivity and specificity attest to the effectiveness of our hematuria CT protocol and support its use.

Adult↗

PubMed2002

Changes in expression of the human homologue of the Drosophila discs large tumour suppressor protein in high-grade premalignant cervical neoplasias.

The Drosophila tumour suppressor discs large (Dlg) is a cell-junction localized protein that is required for the maintenance of epithelial cyto-architecture and the negative control of cell proliferation. The mammalian homologue is likely to have a similar mode of action, and therefore functional perturbation of this protein may be linked to the development of epithelial-derived cancers. The finding that several unrelated viral oncoproteins, including the E6 protein of oncogenic human papillomaviruses, bind to the human homologue of Dlg (hDlg) supports this proposition. Employing immunohistochemistry, we show that in uterine cervical squamous epithelia, prominent localization of hDlg at sites of intercellular contact occurs in cells that have left the proliferating basal cell layers and begun maturation. The presence of hDlg at sites of cell:cell contact diminishes, whilst intracellular cytoplasmic levels increase significantly in high-grade, but not low-grade, cervical neoplasias. In invasive squamous cell carcinomas, total cellular hDlg levels are greatly reduced. Our data suggest that loss of hDlg at sites of intercellular contact may be an important step in the development of epithelial cancers.

Adaptor Proteins, Signal Transducing↗