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Biomedical subjects

R M Schwartz

Publications and source records attributed to R M Schwartz.

At least 19 recordsLinked to original sources

The influence of extra-cellular matrix and stroma remodeling on the productivity of long-term human bone marrow cultures.

The stromal cell layer is believed to play an important role in long-term human bone marrow cultures (LTHBMCs). At present, neither the role that the stromal cell extra-cellular matrix (ECM) plays in influencing stroma behavior is well understood nor are the effects of stroma aging. Rapid medium exchanged LTHBMCs were established on surfaces precoated with human natural fibronectin and type 1 rat tail collagen. Although initial adhesion of hematopoietic cells was improved by the presence of both ECMs, the overall progenitor and nonadherent cell productivity was not improved nor did the stroma grow to confluency faster. Thus, the ECMs used did not significantly influence the cell productivity of LTHBMCs. To examine the influence of stromal cell layer aging, conditioned medium was obtained from the first two weeks of LTHBMCs that was subsequently concentrated and used as a medium supplement in a second set of slowly exchanged LTHBMCs. The presence of the concentrated conditioned medium (conCM) enhanced the production of nonadherent cells three-fold compared with control over an eight week culture period. Control cultures that were exposed to conCM after 4 weeks in culture significantly improved their cell productivity during the latter 4 weeks of culture compared with control. The productivity of cultures exposed to conCM for 4 weeks dropped significantly when unsupplemented medium was used for the latter 4 weeks of culture. Interestingly, phytohemagglutin-stimulated leukocyte-conditioned medium stimulated LTHMBCs in a similar fashion, as did conditioned medium from early LTHBMCs. Taken together, these results strongly suggest that the stromal cell layer does produce important factors for active hematopoiesis during its growth to confluence.

Bone Marrow Cells

In vitro myelopoiesis stimulated by rapid medium exchange and supplementation with hematopoietic growth factors.

We studied the effect of the combination of rapid culture medium exchange with the addition of the human hematopoietic growth factors interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and erythropoietin (Epo) on the proliferation and differentiation of human long-term bone marrow cultures (LTBMCs). Individually and in combinations, IL-3, GM-CSF, and Epo were added to the culture medium of LTBMCs that were maintained with 50% medium volume exchange per day. The combination of IL-3 + GM-CSF + Epo generated the most prolific cultures with an order of magnitude increase in nonadherent cell production from weeks 2 through 8 in culture as compared with unsupplemented controls. Under these conditions, the cultures produced as many cells as were inoculated every 2 weeks and led to a greater than 2.5-fold expansion in terms of the number of nonadherent cells produced over a 6- to 8-week period. Furthermore, the LTBMCs produced nonadherent colony-forming unit-GM (CFU-GM) for more than 20 weeks. The rapid medium exchange combined with the addition of human hematopoietic CSFs significantly enhances the proliferation and differentiation of LTBMCs. These results indicate that addition of combinations of hematopoietic CSFs, together with a rapid medium exchange rate, can provide culture conditions that are suitable for the expansion of the progenitor cell pool and perhaps for the increased survival of hematopoietic stem cells in culture. Although these culture conditions still fall short of full reconstitution of functional human bone marrow, they provide an improved approach to hematopoietic cell culture that may permit the expansion and manipulation of progenitor cells in vitro.

Bone Marrow Cells

The neonatal costs of maternal cocaine use.

OBJECTIVE: --To examine the added neonatal cost and length of hospital stay associated with fetal cocaine exposure. DESIGN: --All cocaine-exposed infants in the study population (n = 355) were compared with a random sample of unexposed infants (n = 199). Regression analysis was used to control for the independent effects of maternal age, smoking, alcohol consumption, prenatal care, race, gravidity, and sex of the infant. SETTING: --A large, public, inner-city hospital studied from 1985 to 1986. PATIENTS: --All infants were routinely tested for illicit substances, records were reviewed for maternal histories of substance abuse, and all known cocaine-exposed singleton infants were included. MAIN OUTCOME MEASURES: --Cost and length of stay until each infant was medically cleared for hospital discharge and cost and length of stay until each infant was actually discharged from the hospital. RESULTS: --Neonatal hospital costs until medically cleared for discharge were $5200 more for cocaine-exposed infants than for unexposed infants (a difference of $7957 vs $2757 [P = .003]). The costs of infants remaining in the nursery while awaiting home and social evaluation or foster care placement increased this difference by more than $3500 (P less than .0001). Compared with other forms of cocaine, fetal exposure to crack was associated with much larger cost increases ($6735 vs $1226). Exposure to other illicit substances in addition to cocaine was also associated with much larger cost increases ($8450 vs $1283). CONCLUSIONS: --At the national level, we estimate that these individual medical costs add up to about $500 million. The large magnitude of these costs indicates that effective treatment programs for maternal cocaine abusers could yield savings within their first year of operation.

Adult

Rapid medium perfusion rate significantly increases the productivity and longevity of human bone marrow cultures.

Long-term in vitro human hematopoietic (Dexter) cultures are limited both in their longevity (8-12 weeks) and in their cell production over time. Hematopoiesis in vivo continues unabated throughout life, suggesting that failure to obtain continuous hematopoiesis in vitro is probably due to the failure of culture conditions to accurately reproduce the in vivo state. Since bone marrow cells in vivo exist at high density and are rapidly perfused by plasma components, we examined the effects of the culture medium perfusion rate and inoculum density on longevity and productivity of human bone marrow cultures. Culture efficiency and longevity were relatively independent of the variation in inoculum density from 10(6) to 5 x 10(6) cells per ml but were significantly altered by the medium perfusion rate. Increased culture perfusion was superior to traditional Dexter schedules, with 0.5 medium volume exchange per day (3.5 volume per week) being optimal. The cultures under these conditions demonstrated an increasing rate of cell production from weeks 4 to 10, with the cell production rate doubling approximately every 2 weeks. Following weeks 10-12 in culture, the cell production rate of all cultures decayed. Production of nonadherent progenitor cells was also highest in cultures perfused at 3.5 medium volume exchanges per week, where progenitor cell production was stable from weeks 6 to 18. The nonadherent cells collected were predominantly macrophages by week 19, except for the cultures perfused at a rate of 3.5 volumes per week and seeded at 5 x 10(6) cells per ml, in which production of granulocytes remained high through week 19. Establishment of more optimal perfusion conditions supports the continuous stable generation of progenitor cells over 5 months in culture, suggesting that primitive stem cells are surviving and proliferating in these cultures.

Bone Marrow Cells

Metabolic effects of three ketogenic diets in the treatment of severe epilepsy.

Pre- and post-prandial circulating concentrations of metabolic fuels and plasma insulin are documented in 59 patients with severe epilepsy while receiving either a normal diet, the classical high-fat ketogenic diet, a medium-chain triglyceride (MCT) diet, or a modified MCT diet. All three therapeutic diets improved the control of epilepsy and induced a significant increase in the concentrations of blood aceto-acetate and 3-hydroxybutyrate, the greatest elevation being seen in patients on the classical diet. The classical diet also caused a significant decrease in blood alanine values, which was not observed with the other therapeutic diets. The only consistent change to occur in all patients on therapeutic diets was an increase in plasma uric-acid. The mechanism by which ketogenic diets improve seizure control remains to be elicited.

Adolescent

An integrated microcomputer system using immobilized cellular electrodes for drug screening.

Biosensors based on immobilized microbial cells were developed for drug screening in our laboratory. Compared with the conventional methods such as diffusion and dilution tests, biosensors have been demonstrated to be superior in sensitivity and require much shorter screening time. An integrated microcomputer system has been developed for data acquisition, database management, and mode of action estimation, which automates the screening processes and reduces the labor requirements significantly.

Anti-Bacterial Agents

The Nordic contribution to the English language twin literature.

This project was inspired by the extensive contribution of Nordic researchers to the English language twin literature. The purpose of the study was to compile a source bibliography of twin literature written at Nordic institutions. The bibliography compiled as a supplement for this paper provides as complete a survey as is possible to obtain in the United States. Our search began with a Medline Computer data base. To make our survey more complete, we cross-referenced and added to this using the Index Medicus, the National Institute of Mental Health Bibliography, Excerpta Medica, specific article references, references provided by Nordic university libraries and Gedda's Estudio dei Gemelli. The full bibliography of 313 references is available at no cost from the Center for the study of multiple Birth, Rm. 476, 333 E. Superior, Chicago, Ill. 60611, U.S.A.

Bibliographies as Topic

Chromosomal mosaicism in amniotic cell culture. A diagnostic Dilemma.

Chromosomal mosaicism, with supernumerary C or C group elements, was observed in the cultured amniotic fluid cells of four fetuses undergoing prenatal diagnosis. There were discrepancies in the karyotypes of cells from different culture flasts of a single fluid sample, between cultures from successive uterine aspirations, and between cultures of amniotic fluid and fetal tissues obtained by pregnancy interruption. Most alarming was the finding, in one case, of identical mosaicism in different culture flasks as well as in repeated amniocenteses derived from a phenytypically normal fetus. In each instance, the aborted fetus or newborn infant proved to be phenotypically and cytogenetically normal. This suggests that mosaicism, demonstrated in cultured amniotic fluid cells, may not reflect the chromosomal constitution of the fetus and may pose a dilemma regarding an accurate diagnosis.

Abortion, Induced