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Biomedical subjects

D Sellers

Publications and source records attributed to D Sellers.

13 recordsLinked to original sources

Human bone marrow stromal cell: coexpression of markers specific for multiple mesenchymal cell lineages.

The role of hematopoietic stem cells in blood cell development is reasonably understood, whereas the identity and the function of bone marrow stromal cells are much less clear. Using stromal cells in bone marrow cultures of the Dexter type, a favorite medium for the study of hematopoiesis, we show that stromal cells actually represent a unique cell type. Conventional wisdom has held that stromal cells in Dexter cultures comprise a mixture of macrophages, hematopoietic cells, adipocytes, osteoblasts, fibroblasts, muscle cells, and endothelial cells. Our findings demonstrate that Dexter cultures consist of three cell types: macrophages ( approximately 35%), hematopoietic cells ( approximately 5%), and nonhematopoietic cells ( approximately 60%). We have purified the nonhematopoietic cells free of macrophages and hematopoietic cells to produce compelling evidence that they in fact represent a single cell type (multidifferentiated mesenchymal progenitor cell, MPC) which coexpresses genes specific for various mesenchymal cell lineages including adipocytes, osteoblasts, fibroblasts, and muscle cells. We further show that these multi- or pluridifferentiated MPCs are capable of supporting hematopoiesis by demonstrating the expression of several hematopoietic growth factors and extracellular matrix receptors including G-CSF, SCF, VCAM-1, ICAM-1, and ALCAM. Since the MPCs can be easily purified to near homogeneity (95%), they can be of value in enhancing engraftment of hematopoietic stem cells. Also, this new understanding of bone marrow stromal cells as "one cell with many different faces" promises to advance our knowledge of regulatory cellular interactions within bone marrow.

Bone Marrow Cells↗

8:45-9:00. Using PET 18F-FDG, 11CO, and 15O-water for Monitoring Prostate Cancer During a Phase II Anti-angiogenic Drug Trial with Thalidomide.

Assessing prostate metastases is difficult with conventional radiographic modalities as few patients have soft tissue involvement and most have only bone lesions. Even with FDG PET, problems due to decreased avidity compared to other tumor types can occur. We assessed PET's ability to monitor changes in such tumors during an anti-angiogenic therapy. We measured changes in tumor blood flow (15O), blood volume (11CO), 18F-FDG uptake and "metabolic volume" before and during thalidomide treatment, to see if these changes correlated with changes in PSA values.Six patients with androgen-independent prostate cancer were imaged with 18F-FDG, 11CO, and 15O water before and during (mean interval 63 days, range 55-76 days) thalidomide therapy (200-1200mg/day). Lesions were visually identified on FDG images (9 bone, 5 soft tissue lesions). VOI's were generated by 3D region growing, with a 50% maximum pixel threshold. These VOI's were registered with, and applied to, the 11CO and water studies. Correlations with PSA values were done using the Spearman rank test.The change in maximum (r = 0.77, p = 0.06) and mean FDG value (r = 0.83, p = 0.03), functional FDG volume (r = 0.66, p = 0.14), and 11-CO blood volume (r = 0.77, p = 0.06) all correlated with the change in PSA. Changes in blood flow values were smaller than the variance of the method for repeated measures, likely due to low flow values in bone.Changes in blood volume measured by 11CO, and the mean and peak activity and functional volume measured by 18F-FDG, correlate with changes in PSA and may be useful in monitoring anti-angiogenic therapy in prostate cancer.

Journal Article↗

Is the circulating ouabain-like compound ouabain?

The evidence is very strong for a circulating inhibitor of the sodium, potassium ATPase in volume-expanded hypertension. Recently, this inhibitor was isolated from human plasma and identified as ouabain. We are reporting our results using a very specific and sensitive immunoassay for ouabain with which we were unable to detect or able to detect only very low levels of circulating immunoreactive ouabain. Immunoassay of 5 mL of human and rat plasma, incubation fluid from bovine and human adrenal cell cultures extracted using a C-18 solid phase column, and HPLC separation did not detect a peak corresponding to ouabain. This procedure could easily detect authentic ouabain added to these extracts at a concentration slightly below that reported to be present by others. The extract from the adrenal cultures had clearly detectable sodium, potassium ATPase using an assay based on inhibition of tritiated ouabain binding to human red cells. Extraction of bovine adrenals detected a very small amount of immunoassayable ouabain which did not elute at a time corresponding to that of ouabain. This study indicates that the postulated sodium, potassium ATPase inhibitor that circulates in plasma is not ouabain, but it is likely to be structurally similar to ouabain, as it appears to cross-react with some antibodies against ouabain.

Adrenal Glands↗

Evaluation of the temperature response to exercise testing in patients with single chamber, rate adaptive pacemakers: a multicenter study.

UNLABELLED: Temperature responsive pacemakers were implanted in 45 patients (ages 44 to 90); 31 patients were evaluated by randomized, paired treadmill exercise tests 1 month postimplant. Of 28 males and 17 females, 19 had coronary artery disease; 8 had congestive heart failure. Pacing indications included sinus node disease (26), atrial fibrillation (15), AV block (10), and brady/tachy syndrome (10); some had multiple indications. Blood temperature (every 10 seconds, resolution = 0.004 degrees C) and pacing rate (every minute) were telemetered from the pacemaker. Average heart rate, exercise duration (5.7 min VVI; 6.7 min VVIR), VVIR response time (22 sec), initial temperature drop (0.23 degrees C) and maximum rate of drop (0.65 degrees C/min), temperature rise (0.31 degrees C VVI; 0.38 degrees C VVIR) and rate of rise (0.27 degrees C/min) were studied in a subset of patients. In pacer-dependent patients, average paired increases in exercise duration and heart rate was 56% and 34%, respectively. Including all (31) patients, some with intermittent sinus rhythm, increases were 28% and 9%, respectively. Because exercise duration increased, temperature rise was higher with rate adaptation. Rate adaptation was obtainable in all patients and patients averaged 99 +/- 48 increases above basic pacing rate per day at nominal temperature sensitivity. CONCLUSION: Beneficial rate adaptation is achievable using blood temperature to modify rate in a sensor based system.

Aged↗

A double-blind, placebo-controlled trial of lithium carbonate therapy for alcoholism.

The efficacy of lithium carbonate as a treatment for alcoholism was examined in a double-blind, placebo-controlled study of 104 men and women meeting DSM-III criteria for alcohol dependence. Subjects entered the study during inpatient treatment and were subsequently followed up for 12 months. Survival analysis disclosed essentially three categories of treatment response: one for noncompliant subjects (0% to 7% abstinent), one for compliant subjects not attaining therapeutic serum lithium levels (31% to 44% abstinent), and one for compliant subjects with therapeutic serum levels (67% abstinent). Two findings led us to believe that therapeutic serum levels of lithium were associated with better outcome over and above a behavioral compliance effect. First, in a dose-response analysis, serum lithium levels and abstinence rates were not linearly associated. Second, all subjects who started lithium carbonate therapy as inpatients were significantly less likely to relapse to drinking during the first month than were placebo-compliant subjects. There was no evidence that depressed alcoholics showed a better treatment response than nondepressed alcoholics or that lithium had any significant impact on the mood or social adjustment of alcoholics. Although the sample size and the difficulties of ascertaining placebo compliance caution against drawing firm conclusions, the data add further support to the hypothesis that lithium has an effect on drinking behavior not related to the treatment of affective symptoms.

Adult↗

Unbiased criteria for severity of depression in alcoholic inpatients.

The internal consistency of the Beck Depression Inventory (BDI) is assessed in 106 inpatient alcoholics by using a latent trait model. The analysis confirms that the BDI measures a single underlying dimension of depressive severity among alcoholics. Seven symptoms discriminate well for severity of depression. These seven--work inhibition, guilt, self-disgust, irritability, indecision, dissatisfaction, and loss of social interest--may represent criteria for depressive severity that are not confounded by chronic drinking, physical withdrawal, unique personality organization, or life circumstances of alcoholics. Three of the symptoms--dissatisfaction, loss of social interest, indecision--may represent core criteria for depressive severity by virtue of their previously demonstrated ability to discriminate well for severity of depression among both psychiatric and medical inpatients.

Adult↗

Evaluation of lithium therapy for alcoholism.

The efficacy of lithium therapy for alcoholism was examined in 84 alcoholic volunteers admitted for rehabilitation. Subjects were randomly assigned to a lithium or placebo treatment condition for 18 months, and were reinterviewed monthly to document their compliance, drinking status, and mood. Two separate factors contributed to abstinent outcome: therapeutic serum lithium levels (greater than or equal to 0.4 mEq/L) and medication compliance. Recommendations are proposed for studying compliance effects in future treatment studies.

Adult↗

Controlling the pink bollworm by disrupting sex pheromone communication between adult moths.

The synthetic sex pheromone (gossyplure) of the pink bollworm was evaporated into the atmosphere of three cotton fields during an entire growing season. The resulting disruption of premating pheromone communication between male and female moths led to a reduction in the population of larvae infesting cotton bolls. This larval control was comparable, in terms of both effectiveness and expense of materials used, to the control achieved in ten comparison fields by growers using conventional insecticide applications.

Animals↗