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Biomedical subjects

S Dow

Publications and source records attributed to S Dow.

9 recordsLinked to original sources
PubMed2001

CD40 stimulation accelerates deletion of tumor-specific CD8(+) T cells in the absence of tumor-antigen vaccination.

Previous work has established a role for CD40-mediated signals in eliciting helper-dependent CD8(+) T cell responses. Here we investigated the effects of in vivo CD40 stimulation on the survival and function of tumor-specific CD8(+) T cells in a mouse melanoma model system. We found that agonistic anti-CD40 antibody treatment alone of tumor-bearing mice accelerated the deletion of tumor-antigen-specific T cells. However, long-term survival and function of tumor-antigen-specific T cells could be achieved when viral immunization with tumor antigen and anti-CD40 treatment were combined. This rescue of CD8(+) T cells could not be easily replicated by inflammatory or antigen-specific stimuli alone, demonstrating the specificity of signals that regulate the deletion or survival of tumor-specific T cells. These results demonstrate that opposing effects can be elicited by CD40 stimulation in vivo and suggest the need for caution in using this treatment for cancer patients.

Animals↗
PubMed2001

The design and testing of a force feedback dental simulator.

The Iowa Dental Surgical Simulator is a haptic simulator to train dental students in the haptic skills of dentistry. The initial design emphasizes the detection of carious lesions. This work describes the software and implementation of the prototype system, the design tradeoffs' and the technical issues associated with haptic and graphics subsystems. The work also describes the current system performance, including a formal evaluation by practicing dentists and performance measures. A discussion of the limitations of the current system is followed by an analysis of opportunities to improve the quality of the simulator. The results should be of interest to designers of medical haptic simulation systems and other simulation designers.

Biophysical Phenomena↗
PubMed2000

Widespread aneuploidy revealed by DNA microarray expression profiling.

Expression profiling using DNA microarrays holds great promise for a variety of research applications, including the systematic characterization of genes discovered by sequencing projects. To demonstrate the general usefulness of this approach, we recently obtained expression profiles for nearly 300 Saccharomyces cerevisiae deletion mutants. Approximately 8% of the mutants profiled exhibited chromosome-wide expression biases, leading to spurious correlations among profiles. Competitive hybridization of genomic DNA from the mutant strains and their isogenic parental wild-type strains showed they were aneuploid for whole chromosomes or chromosomal segments. Expression profile data published by several other laboratories also suggest the use of aneuploid strains. In five separate cases, the extra chromosome harboured a close homologue of the deleted gene; in two cases, a clear growth advantage for cells acquiring the extra chromosome was demonstrated. Our results have implications for interpreting whole-genome expression data, particularly from cells known to suffer genomic instability, such as malignant or immortalized cells.

Aneuploidy↗
PubMed2000

An initial evaluation of the Iowa Dental Surgical Simulator.

The University of Iowa colleges of dentistry and engineering are collaborating to build an effective but low-cost surgical simulator that uses force feedback to teach and assess the tactile skills of dentistry. A prototype simulator was built, and a formative evaluation examined the realism of the haptics and identified directions for future work. Using a cross-over design, twelve experienced practitioners probed two virtual teeth using two instruments attached to the force feedback device. The session was videotaped, the forces recorded, and a standardized questionnaire completed. Two analyses were conducted: an ANOVA examined practitioners' questionnaire responses, and a t-test analyzed the probing forces. Significant tooth order by instrument order interaction and instrument effects were found. Practitioners were generally satisfied. They preferred a standard joystick to an explorer, felt that two-dimensional graphics were sufficient, and emphasized that the existing vibration be eliminated. Random placement of caries should help teach generalized skills.

Analysis of Variance↗
PubMed1998

Cytokine-induced survival of activated T cells in vitro and in vivo.

Many antigen-specific T cells die after exposure to antigen in animals. These cells also die if they are isolated from animals shortly after activation and cultured. Various cytokines were tested for their ability to interfere with this in vitro death. Surprisingly, tumor necrosis factor alpha and other inflammatory cytokines did not prevent the in vitro death of activated T cells, even though these cytokines do prevent activated T cell death in animals. Therefore, the inflammatory cytokines probably act on T cells in vivo via an intermediary factor. Four cytokines, interleukin (IL)-2, IL-4, IL-7, and IL-15, did prevent activated T cell death in vitro, with IL-4 and IL-15 more effective than IL-2 or IL-7. These cytokines share a component of their receptors, the common gamma chain, gammac. Therefore, their collective ability to protect activated T cells from death may be mediated by signals involving gammac. To assess their activity in vivo, two of the cytokines, IL-2 and IL-4, were expressed in animals at local sites of superantigen responses. Both cytokines increased the numbers of T cells found at the local sites 14 days later. Interleukin 4 was more effective than IL-2, even though IL-2 stimulates T cell proliferation better than IL-4. This result suggested that IL-4 and related cytokines can promote T cell survival in vivo as well as in vitro. The ability of these cytokines to prevent the death of activated T cells may be important at certain stages of immune responses in animals.

Animals↗
PubMed1998

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases.

OBJECTIVE: The purpose of this study was to describe the clinical characteristics of a novel group of patients with obsessive-compulsive disorder (OCD) and tic disorders, designated as pediatric autoimmune neuropsychiatric disorders associated with streptococcal (group A beta-hemolytic streptococcal [GABHS]) infections (PANDAS). METHOD: The authors conducted a systematic clinical evaluation of 50 children who met all of the following five working diagnostic criteria: presence of OCD and/or a tic disorder, prepubertal symptom onset, episodic course of symptom severity, association with GABHS infections, and association with neurological abnormalities. RESULTS: The children's symptom onset was acute and dramatic, typically triggered by GABHS infections at a very early age (mean = 6.3 years, SD = 2.7, for tics; mean = 7.4 years, SD = 2.7, for OCD). The PANDAS clinical course was characterized by a relapsing-remitting symptom pattern with significant psychiatric comorbidity accompanying the exacerbations; emotional lability, separation anxiety, nighttime fears and bedtime rituals, cognitive deficits, oppositional behaviors, and motoric hyperactivity were particularly common. Symptom onset was triggered by GABHS infection for 22 (44%) of the children and by pharyngitis (no throat culture obtained) for 14 others (28%). Among the 50 children; there were 144 separate episodes of symptom exacerbation; 45 (31%) were associated with documented GABHS infection, 60 (42%) with symptoms of pharyngitis or upper respiratory infection (no throat culture obtained), and six (4%) with GABHS exposure. CONCLUSIONS: The working diagnostic criteria appear to accurately characterize a homogeneous patient group in which symptom exacerbations are triggered by GABHS infections. The identification of such a subgroup will allow for testing of models of pathogenesis, as well as the development of novel treatment and prevention strategies.

Acute Disease↗
PubMed1997

A controlled trial of light therapy for the treatment of pediatric seasonal affective disorder.

OBJECTIVE: To evaluate the efficacy of light therapy for the treatment of pediatric seasonal affective disorder (SAD). METHOD: 28 children (aged 7 to 17 years) at two geographically distinct sites were enrolled in a double-blind, placebo-controlled, crossover trial of bright-light treatment. Subjects initially entered a week-long baseline period during which they wore dark glasses for an hour a day. They were then randomly assigned to receive either active treatment (1 hour of bright-light therapy plus 2 hours of dawn simulation) or placebo (1 hour of clear goggles plus 5 minutes of low-intensity dawn simulation) for 1 week. The treatment phase was followed by a second dark-glasses phase lasting 1 to 2 weeks. After this phase, the children received the alternate treatment. Response was measured using the parent and child versions of the Structured Interview Guide for the Hamilton Depression Rating Scale, Seasonal Affective Disorders version (SIGH-SAD). RESULTS: Data were analyzed as change from baseline. SIGH-SAD-P total depression scores were significantly decreased from baseline during light therapy compared with placebo (one-way analysis of variance, rho = .009), and no differences were found between the placebo and control phases. Subscores of atypical and typical depression were also significantly decreased during the active treatment (rho = .004 and .028, respectively). A similar trend was noted with the SIGH-SAD-C, but this did not reach significance. At the end of the study, 78% of the parents questioned and 80% of the children questioned rated light therapy as the phase during which the child "felt best." CONCLUSION: Light therapy appears to be an effective treatment for pediatric SAD.

Adolescent↗
PubMed1974

Separation of cells having histochemically demonstrable glucose-6-phosphatase from suspensions of hamster kidney cells in an isokinetic density gradient of Ficoll in tissue culture medium.

Suspensions of enzymatically disaggregated hamster kidney cells were separated primarily according to differences in diameter using velocity sedimentation in a previously described isokinetic density gradient and according to differences in density in an isopycnic density gradient. Cells which contained histochemically demonstrable glucose-6-phosphatase were thought to be cells from proximal tubules and constituted 46.5 +/- 14.1% of the cells in the starting sample suspension of disaggregated kidney cells. The purest gradient fractions from experiments using velocity sedimentation contained 98.0 +/- 0.6% cells which demonstrated glucose-6-phosphatase activity. More than 99.0% of these cells excluded trypan blue. Isopycnic sedimentation was not an effective means of purifying proximal tubule cells.

Animals↗