Burnout syndrome.
Explore the source record for details and available documents.
Burnout, Professional↗
Biomedical subjects
T M Johnson
Publications and source records attributed to T M Johnson.
Dissecting p53 tumor suppressor function in vivo through the analysis of genetically modified mice.
Explore the source record for details and available documents.
Aging, Premature↗
Angular dependent light scattering from multicellular spheroids.
We demonstrate that the effects of cell-cell contact and of changes in cell shape have only a minor effect on the angular distribution of light scattering from mammalian fibroblast cells. This result is important for the development of light scattering as a noninvasive tool for tissue diagnostics such as cancer detection. Changes in cell organization that are not accompanied by changes in internal cellular structure may not be measurable. On the other hand, changes in internal cellular structure should be measurable without interference from changes in overall cellular organization. The second major result of this work is that there are small but significant differences between light scattering of tumorigenic and nontumorigenic cells grown in a three-dimensional culture system. The cause of the differences in light scattering are likely due to the nontumorigenic cells arresting in the G1 phase of the cell cycle, while the tumorigenic cells continue to proliferate.
Animals↗
Polarized angular dependent spectroscopy of epithelial cells and epithelial cell nuclei to determine the size scale of scattering structures.
An understanding of the relationship between tissue structures and light scattering from tissue will help facilitate the development and acceptance of noninvasive optical diagnostics including elastic scattering spectroscopy, diffuse reflectance, and optical coherence tomography. For example, a quantitative model of the structures that scatter light in epithelial cells would allow determination of what structures control the characteristics of in vivo light transport measurements and subsequently could provide a detailed relationship between cellular structures and optical measurements. We have determined the size distribution of refractive index structure variations in epithelial cells as well as in nuclei isolated from epithelial cells from measurements of the angular dependence of polarized light scattering. The quantitative size distributions we obtained for both whole cells and isolated nuclei include particles with effective radii of 2 microm to 10 nm or less and contain orders of magnitude more small particles than large particles. These results demonstrate that not only are biological cells very heterogeneous, but so are the nuclei within them. Light scattering is likely sensitive to structures smaller than those commonly investigated by standard pathology methods.
Animals↗
Cytomegalovirus infection increases development of atherosclerosis in Apolipoprotein-E knockout mice.
Cytomegalovirus (CMV) infection has been associated with coronary artery disease, but it is unknown whether the virus can causally contribute to atherogenesis. To determine whether the virus has this capacity, we infected an atherosclerotic-prone mouse strain (C57BL/6J apoE-/-) with murine CMV. At 14 days of age, 30 mice received CMV (30000 pfu) ip and 30 received virus free media. At 13 and 16 weeks atherosclerotic lesion size was measured from aortic sinus cross-sections. Infection did not alter plasma levels of cholesterol, triglycerides, and high density lipoprotein (HDL); however, 4 weeks after infection IFNgamma levels were elevated (infection vs control: 156+/-49 vs 50+/-22 pg/ml, P=0.04). No differences in lesion size were present at 13 weeks post infection. However, by 16 weeks mean aortic sinus lesion area (mm(2)x10(3)+/-SEM; N=75) in the CMV-infected mice was significantly greater than in uninfected mice (74+/-6 vs 57+/-6; P=0.04). CMV caused the greatest increase (34%) in lesion size in females (103+/-9 vs 77+/-10; P=0.05; N=35). These results provide additional evidence implicating CMV as a causal agent of atherosclerosis, at least in an animal model.
Animals↗
Screening for amblyopia in preverbal children: improved grading criteria for hyperopia.
Explore the source record for details and available documents.
Amblyopia↗
Age-based refinement of referral criteria for photoscreening.
OBJECTIVE: To evaluate examination results from preschool children referred from photoscreening, and to adjust referral criteria for suspected astigmatism. DESIGN: Cross-sectional study and noncomparative case series. PARTICIPANTS: Thirty-one thousand fifty-three preschool children. METHODS: Analysis of (1) referral rate and unreadable photograph rate for all children screened, (2) examination results and treatment plan for all children referred for suspected astigmatism, and (3) examination results and treatment for all referred children aged less than 1 year. MAIN OUTCOME MEASURES: Referral rate, unreadable photograph rate, predictive value positive, treatment plan. RESULTS: The referral rate dropped from 7.8% for children 6 to 11 months to 5.3% for all other ages. The unreadable photograph rate declined exponentially from 12.1% for children aged 6 to 11 months to 1.1% for children aged 4 years. The predictive value positive of a photoscreen referral for all children in the 6- to 11-month age group was 30%, and only 12 of the 94 referred children were treated. The predictive value positive for children less than 1 year of age referred with suspected astigmatism was even lower (25%), and only one child in this age group was treated. The predictive value positive increased with age, and a higher percentage of older children were treated. For children at least 3 years old referred for suspected astigmatism, the predictive value positive was 67% when the examination was performed by a pediatric ophthalmologist. Strabismus, anisometropia, and high hypermetropia were diagnosed in such patients age 2 and older but never in younger children. CONCLUSIONS: Children less than 1 year of age have a much lower pass rate from photoscreening than do older children because of a higher referral rate and higher unreadable rate in this age group. When these children are examined, significant pathosis is usually absent, and intervention is rarely initiated. Most children age 2 and older who are referred for suspected astigmatism have a high likelihood of significant pathosis. It is probably unnecessary to examine children less than age 2 when their photoscreening suggests only astigmatism; conversely, referrals should still be provided for these children when their screening suggests other potentially amblyogenic factors.
Age Factors↗
Urinary incontinence treatment preferences in long-term care.
OBJECTIVE: To elicit preferences for different urinary incontinence (UI) treatments in long-term care (LTC) from groups likely to serve as proxy decision makers for LTC residents. DESIGN: A descriptive, comparative study of preference for UI treatments of frail older adults, family members of nursing home (NH) residents, and LTC nursing staff. Surveys were mailed to families and self-administered by staff. Older adults were interviewed. SETTING: Four LTC facilities and two residential-care facilities in Los Angeles. PARTICIPANTS: Four hundred and three family members of incontinent NH residents were mailed surveys. Sixty-six nursing staff caring for these incontinent residents and 79 older adult residents of care facilities (nine cognitively intact NH respondents and 70 residential care residents) answered surveys. MEASUREMENTS: Preference rankings between seven paired combinations of five different UI treatments were measured on an 11-point visual analog scale, with the verbal anchors "definitely prefer" this treatment, "probably prefer" this treatment, and "uncertain." Respondents gave open-ended comments as well. RESULTS: Forty-two percent of family members (171/ 403) returned the mailed survey. Of all respondents, 85% "definitely" or "probably" preferred diapers, and 77% "definitely" or "probably" preferred prompted voiding (PV) to indwelling catheterization. Respondent groups occasionally differed significantly in their preferences. In choosing between treatment pairs using a visual analogue scale, nurses preferred PV to diapers significantly more than did older adults or families (both of whom preferred diapers) (F (2,295) = 13.11, P < .0001). Older adults, compared with family and nurse respondents, showed a significantly stronger preference for medications over diapers (F (2,296) = 41.54, P < .0001). In open-ended responses, older adults stated that they would choose a UI treatment based in part upon criteria of feeling dry, being natural, not causing embarrassment, being easy, and not resulting in dependence. Nurses said that they would base their choice of UI treatment upon increasing self-esteem and avoiding infection. CONCLUSIONS: Although there was wide variation within and between groups about preferred UI treatment, most respondents preferred noninvasive strategies (diapers and PV) to invasive strategies (indwelling catheters and electrical stimulation). Older adults preferred to a greater degree medications and electrical stimulation, therapies directed at the underlying cause of UI. Despite data documenting that diapering is a less time intensive way to manage UI and that toileting programs are difficult to maintain in LTC, nurses viewed PV as "natural" and strongly preferred it to diapering. Several family members and older adults viewed PV as "embarrassing" and "fostering dependence." These data highlight the need to elicit preferences for UI treatment among LTC residents and their families.
Activities of Daily Living↗
Surgical pearl: the cross-stitch.
Explore the source record for details and available documents.
Humans↗
Guidelines of care for primary cutaneous melanoma.
Explore the source record for details and available documents.
Biopsy↗
Prevalence of factor V Leiden and activated protein C resistance in central retinal vein occlusion.
PURPOSE: Factor V Leiden is a common inherited mutation that is a significant risk factor for deep vein thrombosis. It results in resistance to activated protein C (APC). The association between factor V Leiden and central retinal vein occlusion (CRVO) remains controversial. This study was designed to determine the prevalence of APC resistance and the factor V Leiden mutation in patients with CRVO in a controlled study. METHODS: The study was designed as a case control study conducted in a tertiary care retina practice. The prevalence of APC resistance and factor V Leiden was determined by genetic testing of blood samples obtained from patients with CRVO and clinic control patients. RESULTS: Factor V Leiden was identified in 2.3% of patients with CRVO and 3.5% of clinic control patients. There was no significant association between the presence of factor V Leiden and CRVO (odds ratio, 1.13; 95% confidence interval, 0.65-1.98; P = 0.66). CONCLUSION: Factor V Leiden does not appear to be associated with CRVO. Routine screening of patients with CRVO does not appear to be warranted.
Activated Protein C Resistance↗
Modulation of the catalytic activity of the Src family tyrosine kinase Hck by autophosphorylation at a novel site in the unique domain.
Autophosphorylation is a key event in the activation of protein kinases. In this study, we demonstrate that autophosphorylation of the recombinant Src family kinase Hck leads to a 20-fold increase in its specific enzymatic activity. Hck was found to autophosphorylate readily to a stoichiometry of 1.3 mol of phosphate per mol of enzyme, indicating that the kinase autophosphorylated at more than one site. Solid phase sequencing and two-dimensional mapping of the phosphopeptide fragments derived from the autophosphorylated enzyme revealed that the kinase can undergo autophosphorylation at the following two sites: (i) Tyr-388, which is located to the consensus autophosphorylation site commonly found in the activation loop of many protein kinases, and (ii) Tyr-29, which is located in the unique domain of Hck. Hck purified from mouse bone marrow-derived macrophages could also autophosphorylate in vitro at both Tyr-388 and Tyr-29, indicating that naturally occurring Hck can also autophosphorylate at Tyr-29. Furthermore, Hck transiently expressed in human embryonic kidney 293T cells was found to be phosphorylated at Tyr-29 and Tyr-388, proving that Hck can also undergo autophosphorylation at both sites in vivo. The recombinant enzyme carrying the mutation of Tyr-388 to Phe was also able to autophosphorylate at Tyr-29, albeit at a significantly slower rate. A 2-fold increase in the specific enzymatic activity was seen with this mutant despite the stoichiometry of autophosphorylation only approaching 0.2 mol of phosphate per mol of enzyme. This indicates that autophosphorylation of Tyr-29 contributes significantly to the activation of Hck. Regulation of the catalytic activity by phosphorylation of Tyr-29 in the unique domain may represent a new mechanism of regulation of Src family tyrosine kinases.
Amino Acid Sequence↗
Changes in youth cigarette use and intentions following implementation of a tobacco control program: findings from the Florida Youth Tobacco Survey, 1998-2000.
CONTEXT: Many states are developing tobacco use prevention and reduction programs, and current data on tobacco use behaviors and how these change over time in response to program activities are needed for program design, implementation, and evaluation. OBJECTIVES: To assess changes in youth cigarette use and intentions following implementation of the Florida Pilot Program on Tobacco Control. DESIGN, SETTING, AND PARTICIPANTS: Self-administered survey conducted prior to program implementation (1998), and 1 and 2 years (1999, 2000) later among a sample of Florida public middle school and high school students who were classified as never users, experimenters, current users, and former users of cigarettes based on survey responses. MAIN OUTCOME MEASURES: Changes in cigarette use status, intentions, and behaviors among students over a 2-year period. RESULTS: Surveys were completed by 22,540, 20,978, and 23, 745 students attending 255, 242, and 243 Florida public middle and high schools in 1998, 1999 and 2000, respectively. Response rates for the 3 survey years ranged from 80% to 82% and 72% to 82% for the middle school and high school surveys, respectively. After 2 years, current cigarette use dropped from 18.5% to 11.1% (P<.001) among middle school students and from 27.4% to 22.6% (P =.01) among high school students. Prevalence of never use increased from 56.4% to 69. 3% (P<.001) and from 31.9% to 43.1% (P =.001) among middle school and high school students, respectively. Prevalence of experimenting decreased among middle school and high school students from 21.4% to 16.2% (P<.001) and from 32.8% to 28.2% (P<.001), respectively. Among never users, the percentage of committed nonsmokers increased from 67.4% to 76.9% (P<.001) and from 73.7% to 79.3% (P<.001) among middle school and high school students, respectively. Among experimenters, the percentage of students who said they will not smoke again increased from 30.4% to 42.0% (P<.001) in middle school and from 44.4% to 51.0% (P<.001) in high school. CONCLUSIONS: Progress toward reduction of youth tobacco use was observed in each of the 2 years of Florida's Pilot Program on Tobacco Control. Our results suggest that a comprehensive statewide program can be effective in preventing and reducing youth tobacco use. JAMA. 2000;284:723-728
Adolescent↗
Evidence for leptin expression in fishes.
Tissues from bony fish were screened with anti-mouse leptin antibodies to detect the presence of the fat-regulating hormone in fishes. Low molecular-weight (16 kDa) immunoreactive bands were detected in blood, brain, heart and liver of green sunfish (Lepomis cyanellus), bluegill sunfish (Lepomis macrochirus), largemouth bass (Micropterus salmoides), white crappie (Pomonix annularis), channel catfish (Ictalurus punctatus), and rainbow trout (Oncorhynchus mykiss). To further verify that we had identified leptin, the response of fish "leptin" was measured in fed and fasted green sunfish. Fed sunfish had approximately threefold higher concentration of leptin in blood than did fasted sunfish (fed vs. fasted; 0.599 +/- 0.03 microg/microl vs. 0.196 +/- 0.04 microg/microl; P > F = 0.0001), which is consistent with mammalian models of leptin function. Brain leptin concentration is also positively correlated with percent body fat in white crappie and bluegill. Based upon electrophoretic mobility, immunoreactivity, response to fasting, and correlation with adiposity, we believe we have the first evidence for leptin expression in an ectotherm.
Adipose Tissue↗
Editing data: what difference do consistency checks make?
In 1998, the Florida Department of Health undertook a self-administered school-based survey of tobacco use, attitudes, and behaviors among nearly 23,000 public school students in grades 6-12. The survey design did not use skip patterns; therefore, students had multiple opportunities to contradict themselves. By using examples from the high school portion (grades 9-12) of the survey, the authors examined five possible approaches to handling data inconsistencies and the effect that each has on point estimates. Use of these approaches resulted in point estimates of current cigarette use ranging from 25.6% to 29.7%. The number of missing respondents varied from 33 (less than 1%) to 1,374 (13%), depending on which approach was used. After stratification by gender and race, the prevalence estimates changed marginally for girls but strikingly for boys. Non-Hispanic White students were substantially more likely than non-Hispanic Black students to report current cigarette use, but the magnitude of this difference varied significantly according to the analytical approach used. The approach used to check data consistency may influence point estimates and comparability with other studies. Therefore, this issue should be addressed when findings are reported.
Adolescent↗
Perineural spread of basal cell carcinomas treated with Mohs micrographic surgery.
BACKGROUND: Perineural spread is a well-documented feature of cutaneous tumors and may portend a more aggressive course. The incidence of perineural invasion in basal cell carcinoma (BCC) is reportedly 1%. The authors sought to determine whether perineural spread occurs more commonly than previously thought. METHODS: The authors prospectively evaluated 434 patients with BCC treated with Mohs surgery, assessing the presence or absence of perineural inflammation and invasion in tumors requiring more than one stage of surgery. They also documented the demographic features, clinical characteristics, histologic subtype, and operative data in each case. RESULTS: Seventy-eight BCCs required more than one stage of Mohs surgery. Perineural inflammation, perineural tumor invasion, or both were present in 29 of the 78 tumors (37%), or 6.7% of all 434 prospectively evaluated cases. Twenty-one of the 78 tumors (26.9%) exhibited perineural inflammation, 3 (3.8%) demonstrated perineural invasion, and 5 (6.4%) exhibited both. Tumors with perineural invasion required 5.3 surgical stages on average for clearance, in contrast to tumors without perineural invasion, which required 2.2 stages. Tumors with perineural inflammation, inflammation plus tumor invasion, and invasion alone were, respectively, 138%, 149%, and 194% greater in area preoperatively than tumors without perineural involvement, and their mean defect areas after Mohs surgery were, respectively, 151%, 121%, and 605% larger than those of tumors without perineural involvement. CONCLUSIONS: The incidence of perineural invasion among cases of BCC appears higher than previously recognized. Tumor aggressiveness appears to correlate with the presence of perineural invasion. Surgery with horizontal frozen-section margin control enables easy detection of perineural involvement and should therefore be strongly considered for the treatment of high risk BCC patients.
Aged↗
De novo design of peptides targeted to the EF hands of calmodulin.
This report describes the use of the concept of inversion of hydropathy patterns to the de novo design of peptides targeted to a predetermined site on a protein. Eight- and 12-residue peptides were constructed with the EF hands or Ca(2+)-coordinating sites of calmodulin as their anticipated points of interaction. These peptides, but not unrelated peptides nor those with the same amino acid composition but a scrambled sequence, interacted with the two carboxyl-terminal Ca(2+)-binding sites of calmodulin as well as the EF hands of troponin C. The interactions resulted in a conformational change whereby the 8-mer peptide-calmodulin complex could activate phosphodiesterase in the absence of Ca(2+). In contrast, the 12-mer peptide-calmodulin complex did not activate phosphodiesterase but rather inhibited activation by Ca(2+). This inhibition could be overcome by high levels of Ca(2+). Thus, it would appear that the aforementioned concept can be used to make peptide agonists and antagonists that are targeted to predetermined sites on proteins such as calmodulin.
Amino Acid Sequence↗