Biomedical subjects
Publications and source records attributed to D Demers.
The marrow hematopoietic stem cell is currently being redefined as to all aspects of its phenotype and its total differentiation capacity. This redefinition now includes its plasticity as to production of nonhematopoietic and hematopoietic cell types, the determinants of its in vivo engraftment potential and its expression of stem cell functional characteristics.
Long-term multilineage allochimerism can be obtained in H2-mismatched B6.SJL to BALB/c transplants with host irradiation of 100 cGy, donor spleen cell pre-exposure and costimulator blockade with anti-CD40 ligand (CD40L) antibody. We evaluated this allochimerism approach in murine marrow transplants with different degrees of major histocompatibility complexe (MHC) mismatching; these include: (1) H2-mismatched transplant H2Kk to H2Kb, (2) full haplo-identical transplant H2Kbd to H2Kbk, (3) a partial haplo-identical transplant H2Kd to H2Kbd and (4) an MHC class II mismatch. Levels of chimerism increased up to 12 weeks and then stayed relatively stable up to 1 year after transplant. At 18 weeks post-transplant, the H2-mismatched, haplo-identical, partial haplo-identical and class II-mismatch transplants evidenced 17.9+/-4.4, 40.7+/-0.9, 25.1+/-4.19 and 33.7+/-3.5% donor chimerism, respectively. Dropping the anti-CD40 antibody treatment and spleen cells or changing the schedule of antibody to one injection, in haplo-identical or full-mismatched transplants resulted in no donor-derived chimerism. On the other hand, these still resulted in minor chimerism in class II-mismatched transplants. Lineage analysis of peripheral blood at 6 and 12 months post-transplant demonstrated a significant shift toward increased chimeric lymphocytes and decreased chimeric granulocytes in the full H2 as compared with haplo-identical or class II transplants. Transplantation with anti-CD40L antibody eliminated both graft-versus-leukemia and graft-versus-host disease (GVHD) and delayed lymphocyte infusion did not rescue animals from fatal leukemia. In conclusion, under the conditions of our tolerization regimen, a haplo transplant gives higher engraftment levels than a full H2 mismatch, and despite lower engraftment levels, a class II-mismatched transplant can be successfully accomplished with only 100 cGy and no CD40L blockade.
On the basis of our studies of the fluctuation of the hematopoietic stem cell phenotype with cell cycle trnsit, we hypothesize that the ability of marrow stem cells to convert to nonhematopoietic cells will also vary at different points in the cell cycle. The new biology of stem cells has an impact on many fields including developmental biology and stem cell biology and the clinical potential is enormous.
The need for more or less space is a common laboratory problem. Solutions may include renovating existing space, leaving or demolishing old space, or acquiring new space or property for building. All of these options carry potential environmental risk. Such risk can be the result of activities related to the laboratory facility or property (e.g., asbestos, underground storage tanks, lead paint), or the research associated with it (e.g., radioactive, microbiological, and chemical contamination). Regardless of the option chosen to solve the space problem, the potential environmental risk must be mitigated and the laboratory space and/or property must be decommissioned or rendered safe prior to any renovation, demolition, or property transfer activities. Not mitigating the environmental risk through a decommissioning process can incur significant financial liability for any costs associated with future decommissioning cleanup activities. Out of necessity, a functioning system, environmental due diligence auditing, has evolved over time to assess environmental risk and reduce associated financial liability. This system involves a 4-phase approach to identify, document, manage, and clean up areas of environmental concern or liability, including contamination. Environmental due diligence auditing includes a) historical site assessment, b) characterization assessment, c) remedial effort and d) final status survey. General practice standards from the American Society for Testing and Materials are available for conducting the first two phases. However, standards have not yet been developed for conducting the third and final phases of the environmental due diligence auditing process. Individuals involved in laboratory decommissioning work in the biomedical research industry consider this a key weakness.
Systems dynamics and computer "microworlds" offer a window on the long-term benefit of investing in aggressive care management for patients with non-insulin dependent diabetes mellitus. This article describes how clinicians, planners, payment specialists, and patients collaborated to make the business case for aggressive management of this disease.
Plasmodium falciparum-infected erythrocytes were treated with proteases (trypsin, chymotrypsin, pronase, or V8 protease) or iodinated and the effect of these treatments on the cytoadherent behaviour of the cells was determined. As previously observed, protease treatment reduced cytoadherence. However, it was also found that the P. falciparum-induced adhesin, pfalhesin, was not removed by protease treatment. Gelatin flotation experiments and scanning electron microscopical examination of the treated cells indicated that protease exposure resulted in changes in the knob structures on the cells, which are known to affect the adherent behaviour of the cells. Iodination was found to be an effective method of inactivating pfalhesin.
OBJECTIVE: To determine if maternal alpha fetoprotein (AFP) is elevated in lupus pregnancy and, if so, whether it is associated with treatment or outcome. METHODS: Maternal serum AFP values were obtained once during Weeks 16.3 to 31.7 in 54 pregnancies followed prospectively. AFP was measured by the Maryland State Health Department, who reported the AFP level and a corrected value, multiple of the median (AFP MOM), adjusted for weight, gestational age, and insulin dependent diabetes. Controls were 1001 consecutive samples measured by the same laboratory. RESULTS: AFP MOM was higher in lupus pregnancies (1.425 +/- 0.73 vs 1.169 +/- 0.50, p = 0.001), as were the unadjusted AFP levels (lupus 68.26 +/- 42.2, control 52.49 +/- 27.25, p = 0.001). Of lupus pregnancies 7.4 vs 2.6% of control pregnancies had an abnormal AFP MOM (p = 0.06). The 4 patients with abnormal AFP-MOM, using the 2.3 cutoff, were taking more prednisone (27.25 +/- 18.54 mg vs 10.85 +/- 12.29 mg, p = 0.02), were more likely to have delivered preterm (31.50 +/- 36.31 weeks, p = 0.02), and were more likely to have a high anticardiolipin (aCL) antibody during the pregnancy (p = 0.03). CONCLUSION: AFP is higher in lupus than in control pregnancies, without any increase in neural tube or other birth defects. An abnormal maternal serum AFP level is associated with higher prednisone dose, preterm delivery and aCL. Patients and obstetricians need to be aware that an elevated maternal AFP in lupus pregnancy is not necessarily due to a birth defect, and may be predictive of preterm delivery.
A knobless (K-) line of the FCR-3 isolate of Plasmodium falciparum was obtained by gelatin flotation. Immunofluorescent staining and immunoblots indicated that both the K- line and the K+ (knobby) line from which it was derived contained similar forms of potentially adhesive modified band 3 protein. When the K+ and K- lines were assayed for their cytoadherent and rosetting abilities the K+ line showed a high level of CD36 dependent cytoadherence, whereas the K- line demonstrated a marked pH dependent increase in rosetting. Rosetting was inhibited by the addition of peptides based on band 3 motifs, suggesting that cytoadherence and rosetting involve the same adhesin but that the presence of knobs affects whether the adherent preference of the infected erythrocyte is uninfected red cells or endothelial/C32 amelanotic melanoma cells.
The association of cancer and connective tissue disease is well known, the most frequent being certainly with dermatomyositis. The association cancer and PSS is more controversial. The incidence of neoplasia in that group seems to be comparable with the general population but the proportion of certain types of cancer is different, and the temporal relationship with the apparition of symptoms of PSS is stunning. The hypothesis actually in favor is an imbalance of the immune system, which cause the diminution of the immune surveillance and the apparition of cancer and a concomitant dysregulation of the system, causing the fibrosis of the PSS. We describe a 75 year-old white female who developed a colic adenocarcinoma; she also had, concomitantly, a systemic scleroderma, with sclerodactyly and pulmonary fibrosis. The patient corresponded to the criteria of the American Rheumatism Association for progressive systemic scleroderma (PSS). The prognosis of patients with PSS depends on their systemic involvement but also, we believe, in the more aged group, on the apparition of a neoplasia.
A study on the effects of a laxative jam was done on a group of veterans hospitalized at Le Centre hospitalier de l'Université Laval, Sainte-Foy (Québec). The jam, made up of a mixture of dates and prunes, was tried as a form of treatment to see whether it would increase the frequency of bowel movements and decrease laxative use in long-term care elderly patients. Analysis of the treatment group revealed a significant increase in the frequency of bowel movements and a similar decrease in laxative use. No change was observed in the other patients. Although the addition of this jam amounted to a monthly expense of 167$, it has remained part of the diet on a PRN basis.
Tibial fractures are relatively frequent injuries of young children. These fractures are occasionally the cause of a childhood gait disturbance. Additionally, tibial fractures may be the result of child abuse. Consequently, the pediatrician should have knowledge concerning these injuries. In this paper, we present a review of tibial fractures in hospitalized children and describe their associations with nonaccidental trauma (NAT). Finally, we provide suggestions for improving nonmenclature clarity for isolated spiral fractures of the tibia.
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The purpose of this study was to determine if inhalation of mainstream (MS) or sidestream (SS) smoke affects the reproductive organs of female hamsters. Females inhaled smoke from one or two cigarettes twice per day for 30 d prior to mating using a smoking machine equipped for nose breathing. Serum cotinine levels were within the ranges found in active and passive humans smokers. On day 7 of pregnancy, the reproductive organs of controls and smokers were evaluated for the total number of corpora lutea (CL), the percentage of normal, pink, and small CL, the vascular area in the CL, the ultrastructure of the oviductal epithelium, the ratio of ciliated to secretory cells in the ampulla of the oviduct, the stretchability of the uterine horns, the percentage of implantation sites, and the percentage of touching implantation sites. All parameters, except the percentages of implantation sites and of small CL, were affected by exposure to smoke. To determine if the effects of smoking on the ovary and uterus could be reversed, females smoked for 30 d, remained in their cages without smoking for 30 d, and then were mated and evaluated on day 7 of pregnancy. In this reversal experiment, all ovarian and uterine parameters (except total CL) previously affected by smoking were normal in MS and SS females. These experimental observations show that components in both MS and SS smoke, when delivered at levels comparable to those human smokers receive, can affect the ovary, oviduct, and uterus.