Biomedical subjects

D D Duncan

Publications and source records attributed to D D Duncan.

At least 19 recordsLinked to original sources

PubMed1999

Digital image capture and automated analysis of posterior capsular opacification.

PURPOSE: To develop and validate a digital imaging and analysis technique for assessing the extent of posterior capsular opacification after cataract surgery. METHODS: Retroillumination images of the posterior capsule were obtained by using a digital camera mounted on a slit lamp. The images were analyzed using an available image analysis software program. The image acquisition and analysis techniques were tested for face validity, reproducibility, and the ability to detect progression of capsular opacity over time. RESULTS: Digital retroillumination images were obtained without patient discomfort. Automated analysis of images correlated well with clinical grading both at slit lamp examination and when looking at the images themselves (Spearman's correlation coefficient >0.7). Analysis of images taken at different times showed high reproducibility (intraclass correlation >0.9), and the system was able to identify progression of capsular opacity over a 2-year period with a mean increase of 15.8% in progressors versus an increase of 0.6% in nonprogressors (P < 0.05). CONCLUSIONS: Digital retroillumination images of the posterior capsule can be obtained reliably, and automated analyses correlate well with clinical assessment. The system presented here uses commercially available instruments and software, and it is practical for use in longitudinal studies of posterior capsule opacification. It is reliable, easy to use, and can detect small changes in the percentage area covered by posterior capsule opacification over time.

Cataract↗

PubMed1998

Racial differences in lens opacities: the Salisbury Eye Evaluation (SEE) project.

The purpose of this study was to determine racial differences in the prevalence of different types of lens opacities and cataract surgery. Between 1993 and 1995, the Salisbury Eye Evaluation (SEE) Project enrolled a representative sample of 2,520 community-dwelling persons aged 65-84 years in Salisbury, Maryland, 26.4% of whom were African-American. Participants received a full eye examination, and photographs were taken for documentation of lens status. Photographs were graded using a standardized grading system for the presence of cortical, nuclear, or posterior subcapsular cataract (PSC) opacification in at least one eye. The odds of having cortical opacities were 4.0 times greater among African Americans than among Caucasians (95% confidence interval (CI) 3.3-4.8). Caucasians were significantly more likely to have nuclear opacities (odds ratio = 2.1, 95% CI 1.7-2.6) and PSC opacities (odds ratio = 2.5, 95% CI 1.7-3.6). The odds of cataract surgery were 2.8 times higher among Caucasians, but these differences did not explain the differences in the prevalence of different types of lens opacities by racial group. With lower rates of nuclear and PSC opacities than Caucasians, African Americans may have a lower demand for cataract surgery. However, even with these differences, there is still significant unnecessary loss of vision due to cataract among older African Americans, for whom programs to ensure access to surgical care are indicated.

Aged↗

PubMed1998

Sunlight exposure and risk of lens opacities in a population-based study: the Salisbury Eye Evaluation project.

CONTEXT: Exposure to UV-B radiation in sunlight has been shown to increase the risk of cataract formation in high-risk occupational groups, but risk to the population has not been quantified. OBJECTIVES: To determine the ocular exposure to UV-B radiation in sunlight for a population of older persons and to determine the association between UV-B and lens opacities. DESIGN: The Salisbury Eye Evaluation project, a population-based cohort of older adults. SETTING: Salisbury, Md. PARTICIPANTS: A total of 2520 community-dwelling 65-year-old to 84-year-old adults in Salisbury, Md, from 1993 to 1995, of whom 26.4% were African Americans. MAIN OUTCOME MEASURE: Association of photographically documented cortical opacity 3/16 or greater in at least 1 eye with ocular UV-B exposure, reported in Maryland sun-years of exposure. RESULTS: The odds of cortical opacity increased with increasing ocular exposure to UV-B (odds ratio [OR], 1.10; 95% confidence interval [CI], 1.02-1.20). The relationship was similar for women (OR, 1.14; 95% CI, 1.00-1.30) and for African Americans (OR, 1.18; 95% CI, 1.04-1.33). Analyses of the ocular dose by each age group after the age of 30 years showed no vulnerable age group, suggesting damage is based on cumulative exposure. CONCLUSIONS: Although this population of older Americans has relatively low ocular exposure to UV-B in sunlight, there is still an association between ocular exposure and increasing odds of cortical opacity. Our study found an association among African Americans, which, to our knowledge, has not been reported previously. All sex and racial groups would benefit from simple methods to avoid ocular sun exposure.

Aged↗

PubMed1997

Positive selection induces CD4 promoter and enhancer function.

Developmental expression of the CD4 gene in mature T cells is controlled by at least four transcriptional control elements: a promoter, two enhancers and a silencer. In this report we use a transgenic approach to study the mechanisms in which these elements interact to convey appropriate tissue- and cell-specific expression at all stages of T cell development. Our data indicate that the control of CD4 gene expression requires the interaction of multiple elements functioning in different combinations at different stages of T cell development. Expression of the CD4 gene in immature CD4+CD8+ thymocytes requires a third enhancer element located in the 3' flanking region of the CD4 gene. Interestingly, the CD4 promoter and proximal/distal enhancers first begin to function at the HSAlo CD69lo H-2Khi CD4 single-positive stage; cells of this phenotype are believed to have survived positive selection. These data indicate that the CD4 promoter and late enhancer elements are induced by positive selection; thus, the final maturation process is an active event that requires the initiation of a novel program of gene expression.

Animals↗

PubMed1997

Assessment of ocular exposure to ultraviolet-B for population studies. Salisbury Eye Evaluation Project Team.

We have developed an empirical model with which to estimate the ocular exposure in the UVB wavelength band. This model incorporates aspects of personal behavior, geographic location, season and wavelength that have been developed from population-based data. This model, in conjunction with job history interviews, allows the estimate of cumulative exposures from age 30 in our population-based study. We present data on average annual exposure by age, gender, race, education and reported photophobia. The exposures in the general population are considerably lower than exposures reported in previous works based on occupational groups. There is a statistically significant difference between males and females, with females having lower exposures. African-Americans have median exposures similar to whites. Exposures decrease with education and with reported photophobia. These data provide the basis for characterizing lifetime exposure for the general population. The variability of exposure is much greater than found in occupational groups and includes numbers in the lowest exposure. The model should permit determination of a dose-response relationship with eye disease, even to the lower dose ranges.

Adult↗

PubMed1997

New objective classification system for nuclear opacification.

We have developed an autonomous objective classification scheme for degree of nuclear opacification. The algorithm was developed by using a series of color 35-mm slides acquired with a Topcon photo slit-lamp microscope and use of standard camera settings. The photographs were digitized, and first, and second-order gray-level statistics were extracted from within circular regions of the nucleus. Classifications of severity were performed by using these features as input to a neural network. Training versus classification performance was tested by using photographs of different eyes, and test/retest classification reproducibility was evaluated by using paired photographs of the same eyes. We demonstrate good performance of the classifier against subjective assessments rendered by the Wilmer grading system [Invest. Ophthalmol. Visual Sci. 29, 73 (1988)] and markedly better test/retest reproducibility.

Algorithms↗

PubMed1997

Visible and ultraviolet-B ocular-ambient exposure ratios for a general population. Salisbury Eye Evaluation Project Team.

PURPOSE: To estimate the numerical value of the ocular-ambient exposure ratio (OAER) (ratio of the facial exposure to that on a horizontal plane) as a function of wavelength band, season, and job category and to establish the effect of various modifiers, such as geography and the use of hats, for use in general population studies. METHODS: Two hundred sixty-four persons within several job categories representing the jobs in our Salisbury, Maryland, population were instrumented with ultraviolet-B (UVB) and visible band sensors for 1 complete day. Studies were done over all four seasons, both with and without hats. RESULTS: OAERs in the UVB wavelength band generally are higher than in the visible (13% versus 6%), display no significant variation with job category, show a seasonal effect (highest in the winter-spring [18%], lowest in the summer [10%], and intermediate in the fall [14%]), and are reduced 34% by the use of hats. In the visible wavelength band, OAERs are affected weakly by job function, although this variation is not significant, display a seasonal effect with three seasons as in the UVB, and are not affected significantly by the use of hats. In neither the UVB nor the visible portions of the spectrum did the authors find an effect on the OAER due to photophobia or eye color. CONCLUSIONS: With the authors' exposure model, the authors have at their disposal a valuable tool for exploring the relation between UVB, UVA, and visible radiation and a number of age-related eye diseases.

Environmental Exposure↗

PubMed1996

Asymmetric redundancy in CD4 silencer function.

We and others have defined a transcriptional silencer critical for the proper expression of the CD4 gene at all stages of T cell development. In this report, we use biochemical techniques to identify three different factor-binding sites within the CD4 silencer, denoted sites I, II, and III. Using transgenic analyses, we determine that although all three factor-binding sites are important for silencer activity, there is significant redundancy in that the presence of either site II alone, or the combination of sites I and III permits silencer function. Thus, our data indicate that the mechanism of function of the CD4 silencer is extremely complex. Further biochemical analyses indicate that the factor binding to site II has the same sequence specificity as a factor binding to an E box site in the CD4 enhancer; thus, a member of the bHLH factor family may be important in mediating silencer function.

Animals↗

PubMed1995

Results of ophthalmic examinations of 29 alpacas.

Analysis of the results of ophthalmic examinations of 29 alpacas (Lama pacos) revealed a direct relationship among coat color, iris color, and ocular fundus pigmentation. Alpacas with light-pigmented coats had iris color that included combinations of gray, blue, and brown, and had reduced pigmentation of the ocular fundi. Alpacas with dark coats had brown irides and pigmented ocular fundi. Eleven alpacas had evidence of ophthalmic conditions, including bilateral conjunctivitis (1); formation of a superficial corneal scar (1); formation of posterior synechiae and anterior cataracts (4); development of a deep corneal scar with anterior synechiae, buphthalmia, a subluxated lens, and cataracts (1); development of focal incipient primary cataracts (2); formation of vitreous opacities (1); and development of a unilateral optic nerve coloboma (1).

Animals↗

PubMed1995

Noncontact microstrain measurements in orthodontic wires.

A technique is presented that allows for highly sensitive and highly accurate measurements of microstrain in biomaterials. It is particularly useful for measuring strains in materials where the use of conventional extensometers or strain gauges is impracticable, such as reinforcement fibers and orthodontic wires and in hostile environments. The technique is based on the well known technique of observing translating laser speckle with a linear-array charge-coupled device (CCD) camera. However, it employs a relatively new data processing algorithm involving a two-dimensional frequency transform of the data. Advantages of the technique include: insensitivity to slow surface microstructure changes, insensitivity to zero-mean noise processes, compact design, modest resolution requirements, and the fact that it is truly noncontact. Strain rate measurements were made on an 0.028-gauge round stainless steel orthodontic wire as an example of this technique. The Young's modulus of the wire based on the speckle technique was 2.04 x 10(11) Nm(-2), which is very close to the textbook value.

Algorithms↗

PubMed1995

The development of personal dosimeters for use in the visible and ultraviolet wavelengths regions. The Salisbury Eye Evaluation Team.

We have designed, developed, and field evaluated a two-part personal dosimeter for estimating ocular exposure to visible and ultraviolet radiation. The detector head id compact enough to be mounted on the bow of eyeglass frames, and the recorder is small enough to be carried in a shirt pocket. The detector head consists of a silicon photodiode with filter (Schott glass GG400) and diffuser for visible light measurements and a polysulphone film badge for ultraviolet-B (UVB, 290-320 nm) measurements. The measurements correspond well to those obtained using ambient monitors and should be useful for studies of ocular UVB exposure.

Equipment and Supplies↗

PubMed1995

A Myc-associated zinc finger protein binding site is one of four important functional regions in the CD4 promoter.

The CD4 promoter plays an important role in the developmental control of CD4 transcription. In this report, we show that the minimal CD4 promoter has four factor binding sites, each of which is required for full function. Using biochemical and mutagenesis analyses, we determined that multiple nuclear factors bind to these independent sites. We determined that an initiator-like sequence present at the cap site and an Ets consensus sequence are required for full promoter function. We also demonstrate that the Myc-associated zinc finger protein (MAZ) appears to be the predominant factor binding to one of these sites. This last site closely resembles the ME1a1 G3AG4AG3 motif previously shown to be a critical element in the P2 promoter of the c-myc gene. We therefore believe that the MAZ transcription factor is also likely to play an important role in the control of developmental expression of the CD4 gene.

Base Sequence↗

PubMed1995

Ocular and dermatologic health effects of ultraviolet radiation exposure from the ozone hole in southern Chile.

OBJECTIVES: This study sought to investigate numerous reports emanating from Punta Arenas, Chile (population 110,000, latitude 53 degrees S), that associated acute ocular and dermatologic disease in humans and animals with excess ultraviolet-B (UV-B) exposure in the setting of the thinning of the ozone column. METHODS: Ophthalmologic and dermatologic records in Punta Arenas were systematically reviewed to enumerate sentinel diagnoses potentially associated with UV-B exposure, ocular examinations on representative animal populations were performed, and the ambient UV-B exposure in the region during the time of maximal thinning was estimated. RESULTS: No increase in patient visits or conditions attributable to UV-B exposure was seen for periods of known ozone depletion compared with control periods. Although ambient UV-B exposure was 1.6 to 2.3 times the habitual exposure on individual days, this excess exposure conferred only a 1% increase in annual exposure on the region. CONCLUSION: This study does not support existing lay reports of ocular and dermatologic disease in humans and animals that had been associated with the ozone hole over southern Chile.

Animals↗

PubMed1994

A transcriptional silencer controls the developmental expression of the CD4 gene.

The appropriate expression of the CD4 glycoprotein is required for T-cell function and development. Here we define the transcriptional control elements in the CD4 locus that convey CD(4+)-specific expression of a marker gene in transgenic mice. Using nuclear run-on experiments, we have determined that the major mechanism for CD4 expression control during development is transcriptional. We have identified a developmental stage- and tissue-specific negative regulatory element in the first intron of the murine CD4 gene that has the characteristics of a transcriptional silencer. The CD4 silencer functions to inhibit marker gene expression at two different stages of T-cell development, as well as in non-T hematopoietic cells, and thus is the critical controlling element responsible for T-cell-specific, as well as developmental- and subclass-specific, expression.

Animals↗

PubMed1994

Role of antigen-presenting cells in the polarized development of helper T cell subsets: evidence for differential cytokine production by Th0 cells in response to antigen presentation by B cells and macrophages.

Immune challenges can elicit polarized responses skewed towards the development of T helper type 1 (Th1) or Th2 T cell subsets. To determine if distinct antigen-presenting cells (APC) populations might selectively influence Th subset development, we studied the role of two key APC populations, B cells and macrophages, in the differentiation of effector Th populations from naive precursor Th in vitro. Antigen (Ag)-specific, naive CD4+ T cells were enriched from a mouse strain, AND, bearing a transgenic alpha/beta T cell receptor (TCR) encoding reactivity with pigeon cytochrome c peptide 88-104. Peptide Ag was used throughout these studies so that differences in the uptake and processing by the two APC populations would not influence the results. Both APC populations, activated B cells and bone marrow-derived macrophages, supported the development of effector Th having the capacity to secrete high levels of cytokines when restimulated. Regardless of APC population present during effector development, exogenous interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) had dominant effects on Th subset development. Thus, with both APC populations, effector Th generated in the presence of IFN-gamma acquired a Th1-type cytokine profile, Th generated with IL-4 acquired a Th2-type cytokine profile, and Th generated without IFN-gamma or IL-4 acquired a Th0-type cytokine profile. B cells and macrophages also had equivalent APC function in the restimulation of Th1 and Th2-like effectors, since only minor differences in cytokine production were noted for these effector populations when restimulated with the two APC populations. However, in 8 of 19 experiments, the Th0-like effector population generated in the presence of IL-2 differentially responded to restimulation with B cells and macrophages, secreting significantly more IFN-gamma when restimulated with B cells, and significantly more IL-4 when restimulated with macrophages. We also found that Th effector populations recultured in IFN-gamma or IL-4 assumed a more Th1 or Th2-like phenotype, respectively, regardless of their initial cytokine profile. We conclude that through a subtle capacity to skew cytokine production by a Th0 subset, different APC may selectively influence Th subset development under conditions of prolonged or chronic stimulation in an autocrine fashion.

Animals↗

PubMed1993

Memory effectors: a potent, IL-4-secreting helper T cell population that develops in vivo after restimulation with antigen.

Resting CD4+ memory T cells from the spleens of mice primed more than 6 wk earlier with KLH in adjuvant produce IL-2 and IL-3, but only low levels of IL-4 and IFN-gamma, and undetectable IL-5 after specific restimulation in vitro. In contrast, when previously primed mice are boosted by i.v. injection of soluble KLH, a CD4+ T cell population develops in the spleen that can produce greatly increased levels of IL-4, and variably increased IL-2, IFN-gamma, and/or IL-3. The ability of these memory effector Th cells to be restimulated to secrete cytokines is maximal by 3 days after in vivo boosting with Ag, and declines rapidly thereafter. Memory effector Th are induced in the spleens of KLH-primed mice that have been depleted of precursor T cells by thymectomy more than 25 wk previously, suggesting that they are derived from a memory T cell population. Cell separation on the basis of CD45RB or MEL-14, surface markers that are down-regulated on memory CD4+ cells, indicates that memory effector Th are in the CD45RBlo and MEL-14- subsets of CD4+ T cells. The frequency of KLH-specific splenic CD4+ T cells with the capacity to secrete cytokines in limiting dilution cultures is very low in unprimed mice (1/3 x 10(4) to 1/9 x 10(4)), but increases as much as 50-fold after priming. IL-2, but not IL-4, can be detected in the supernatants of stimulated unprimed CD4+ T cells. Both IL-2- and IL-4-producing cells are readily detected after priming, and frequencies of IL-2-secreting cells (1/250 to 1/4000) are up to ninefold greater than those for IL-4 secreting cells. Boosting elicits variable (two to eightfold) increases in the frequencies of both IL-2- and IL-4-producing CD4+ T cells. However, high IL-4 titers associated with memory effector Th function can be obtained when significant frequency changes are not detected after boosting. The data suggest that reactivation of resting memory Th in vivo induces their differentiation into effector Th with the capacity to secrete much higher levels of IL-4. Although the capacity to produce high levels of IL-4 is associated with both primary and memory CD4+ effector populations, memory effector Th are the higher producers.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1992

Response of naive antigen-specific CD4+ T cells in vitro: characteristics and antigen-presenting cell requirements.

Because of the low frequency of T cells for any particular soluble protein antigen in unprimed animals, the requirements for naive T cell responses in specific antigens have not been clearly delineated and they have been difficult to study in vitro. We have taken advantage of mice transgenic for the V beta 3/V alpha 11 T cell receptor (TCR), which can recognize a peptide of cytochrome c presented by IEk. 85-90% of CD4+ T cells in these mice express the transgenic TCR, and we show that almost all such V beta 3/V alpha 11 receptor-positive cells have a phenotype characteristic of naive T cells, including expression of high levels of CD45RB, high levels of L-selectin (Mel-14), low levels of CD44 (Pgp-1), and secretion of interleukin 2 (IL-2) as the major cytokine. Naive T cells, separated on the basis of CD45RB high expression, gave vigorous responses (proliferation and IL-2 secretion) to peptide antigen presented in vitro by a mixed antigen-presenting cell population. At least 50% of the T cell population appeared to respond, as assessed by blast transformation, entry into G1, and expression of increased levels of CD44 by 24 h. Significant contributions to the response by contaminating memory CD4+ cells were ruled out by demonstrating that the majority of the CD45RB low, L-selectin low, CD44 high cells did not express the V beta 3/V alpha 11 TCR and responded poorly to antigen. We find that proliferation and IL-2 secretion of the naive CD4 cells is minimal when resting B cells present peptide antigen, and that both splenic and bone marrow-derived macrophages are weak stimulators. Naive T cells did respond well to high numbers of activated B cells. However, dendritic cells were the most potent stimulators of proliferation and IL-2 secretion at low cell numbers, and were far superior inducers of IL-2 at higher numbers. These studies establish that naive CD4 T cells can respond vigorously to soluble antigen and indicate that maximal stimulation can be achieved by presentation of antigen on dendritic cells. This model should prove very useful in further investigations of activation requirements and functional characteristics of naive helper T cells.

Animals↗

PubMed1992

Effects of arterial compliance and non-Newtonian rheology on correlations between intimal thickness and wall shear.

A minimally diseased (mean intimal thickness = 56 microns) human aortic bifurcation was replicated in rigid and compliant flow-through casts. Both casts were perfused with physiological flow waves having the same Reynolds and unsteadiness numbers; the pulse pressure in the compliant cast produced radial strains similar to those expected from post-mortem measurements of the compliance of the original tissue. The compliant cast was perfused with a Newtonian fluid and one whose rheology was closer to that of blood. Wall shear rate histories were estimated from near-wall velocities obtained by laser Doppler velocimetry at identical sites in both casts. Intimal thickness was measured at corresponding sites in the original vessel and linear regressions were performed between these thicknesses and several normalized shear rate measures obtained from the histories. The correlations showed a positive slope--that is, the intima was thicker at sites exposed to higher shear rates--consistent with earlier results for relatively healthy vessels, but their significance was often poor. There was no significant effect of either model compliance or fluid rheology on the slopes of the correlations of intimal thickness against any normalized shear rate measure.

Aorta↗