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Biomedical subjects

D Witherspoon

Publications and source records attributed to D Witherspoon.

17 recordsLinked to original sources

Tractional force generation by porcine Müller cells: stimulation by growth factors in human vitreous.

PURPOSE: To examine the levels of Müller cell contraction-stimulating activity in human vitreous, correlate these levels with clinical presentation, and identify, the causative growth factors. METHODS: Human vitreous was collected from patients undergoing pars plana vitrectomy (n = 84). Müller cells were isolated from porcine retina and maintained in tissue culture. Tractional forces generated by cells incubated on three-dimensional collagen gels were measured as changes in gel thickness. Contraction-stimulating activity in vitreous (VA) was calculated from the close-response profiles of gel contraction to vitreous protein. The contributions of individual growth factors to vitreous activity (n = 10) were assessed by inhibition with specific neutralizing antibodies. RESULTS: The mean VA of patients with retinal detachment (3.65) and proliferative vitreoretinopathy stages A, B, and C (2.06) were elevated above that of patients without retinal pathology (vitreous activity = 0.23) or retinal defects alone (0.57). Mean activities in patients with epimacular proliferation (1.22) and vitreous hemorrhage (1.40) were also significantly elevated. The percentage of this activity attributable to insulin-like growth factor 1 (IGF-1) varied from 9.2% to 84.5% with a mean of 61.3%. Similarly, the percent contribution of platelet-derived growth factor (PDGF) ranged from 6.8% to 49.0% with a mean of 26.5%. CONCLUSIONS: The vitreous of patients with retinal detachment, proliferative retinal disease, and vitreous hemorrhage contain varying amounts of growth factors that stimulate tractional force generation by Müller cells. The majority of the activity can be attributed to IGF-1 and a smaller proportion to PDGF.

Animals↗

Internal eliminated sequences interrupting the Oxytricha 81 locus: allelic divergence, conservation, conversions, and possible transposon origins.

Internal eliminated sequences (IESs) often interrupt ciliate genes in the silent germline nucleus but are exactly excised and eliminated from the developing somatic nucleus from which genes are then expressed. Some long IESs are transposons, supporting the hypothesis that short IESs are ancient transposon relics. In light of that hypothesis and to explore the evolutionary history of a collection of IESs, we have compared various alleles of a particular locus (the 81 locus) of the ciliated protozoa Oxytricha trifallax and O. fallax. Three short IESs that interrupt two genes of the locus are found in alleles from both species, and thus must be relatively ancient, consistent with the hypothesis that short IESs are transposon relics. In contrast, TBE1 transposon interruptions of the locus are allele-specific and probably the results of recent transpositions. These IESs (and the TBE1s) are precisely excised from the DNA of the developing somatic macronucleus. Each IES interrupts a highly conserved sequence. A few nucleotides at the ends of each IES are also conserved, suggesting that they interact critically with IES excision machinery. However, most IES nucleotide positions have evolved at high rates, showing little or no selective constraint for function. Nonetheless, the length of each IES has been maintained (+/- 3 bp). While one IES is approximately 33 bp long, three other IESs have very similar sizes, approximately 70 bp long. Two IESs are surrounded by direct repeats of the sequence TTCTT. No other sequence similarities were found between any of the four IESs. However, the ends of one IES do match the inverted terminal repeat consensus sequence of the "TA" IESs of Paramecium. Three O. trifallax alleles appear to have been recipients in recent conversion events that could have been provoked by double-strand breaks associated with IES ends subsequent to IES transposition. Our findings support the hypothesis that short IESs evolved from ancient transposons that have lost most of their sequences, except those necessary for precise excision during macronuclear development.

Alleles↗

Pathologic human vitreous promotes contraction by fibroblasts. Implications for proliferative vitreoretinopathy.

OBJECTIVE: To establish and quantify the presence of contraction-stimulating activity in pathologic vitreous and correlate this activity with clinical presentation and outcome, especially with proliferative vitreoretinopathy. METHODS: Contraction-stimulating activity of vitreous collected during surgery was quantified with a tissue culture assay using fibroblasts as target cells. The activity of each sample was correlated with patient history, clinical presentation, risk factors, proliferative disease, and postoperative proliferation. RESULTS: Pathologic vitreous contained measurable quantities of contraction-stimulating activity and stimulated contraction in vitro, with elevated activities in samples from patients with proliferative vitreoretinopathy, epimacular proliferation, retinal detachment, retinal defects, pigmented cells in the vitreous, hemorrhage, or uveitis. Patients with postoperative proliferation had significantly elevated mean activities. CONCLUSIONS: Levels of contraction-stimulating activity in pathologic vitreous correlate with some risk factors for the development of proliferative vitreoretinopathy and may ultimately be useful in the assessment of disease severity and the prediction of postoperative proliferation.

Adolescent↗

Contextual cuing and memory performance in brain-damaged amnesics and old people.

In Experiment 1, groups of Korsakoff amnesics and alcoholic controls learned a list of paired-associate words in a standard testing room or in a room with distinctive contextual features. Recall was tested 48 hr later in the same or other context. This procedure was repeated in Experiment 2 with old people living in institutions or in the community, but matched for age, health, education, and socioeconomic background. The amnesic patients and institutionalized old people, relative to their comparison groups, were more impaired in recalling the lists under standard conditions and were more responsive to contextual cuing, especially when the distinctive cues were provided during original learning. The results highlight the susceptibility to interference of Korsakoff amnesics and institutionalized old people and offer further evidence that both groups are more responsive to salient contextual cues than either young people or old people living in the community.

Aged↗

Evaluating research in worksite health promotion.

Critical review of studies published in the area of worksite health promotion is an important skill for health promotion professionals. Most studies have some weaknesses which make it difficult to draw meaningful conclusions. Therefore, it is important to consider the research design of these studies. By accurately evaluating the conclusions of health promotion investigations, health promotion professionals will be able to make better recommendations for effective program development.

Evaluation Studies as Topic↗