Biomedical subjects

L Francisco

Publications and source records attributed to L Francisco.

6 recordsLinked to original sources

PubMed2006

Prevalence of conception and pregnancy outcomes after hematopoietic cell transplantation: report from the Bone Marrow Transplant Survivor Study.

We conducted a retrospective study to describe the magnitude of compromise in reproductive function and investigate pregnancy outcomes in 619 women and partners of men treated with autologous (n=241) or allogeneic (n=378) hematopoietic cell transplantation (HCT) between 21 and 45 years of age, and surviving 2 or more years. Median age at HCT was 33.3 years and median time since HCT 7.7 years. Mailed questionnaires captured pregnancies and their outcomes (live birth, stillbirth, miscarriage). Thirty-four patients reported 54 pregnancies after HCT (26 males, 40 pregnancies; eight females, 14 pregnancies), of which 46 resulted in live births. Factors associated with reporting no conception included older age at HCT (> or =30 years: odds ratio (OR)=4.8), female sex (OR=3.0), and total body irradiation (OR=3.3). Prevalence of conception and pregnancy outcomes in HCT survivors were compared to those of 301 nearest-age siblings. Although the risk for not reporting a conception was significantly increased among HCT survivors (OR=36), survivors were not significantly more likely than siblings to report miscarriage or stillbirth (OR=0.7). Although prevalence of conception is diminished after HCT, if pregnancy does occur, outcome is likely to be favorable. Patients should be counseled prior to transplant regarding strategies to preserve fertility.

Adult↗

PubMed2000

Consequences of cell death: exposure to necrotic tumor cells, but not primary tissue cells or apoptotic cells, induces the maturation of immunostimulatory dendritic cells.

Cell death by necrosis is typically associated with inflammation, in contrast to apoptosis. We have identified additional distinctions between the two types of death that occur at the level of dendritic cells (DCs) and which influence the induction of immunity. DCs must undergo changes termed maturation to act as potent antigen-presenting cells. Here, we investigated whether exposure to apoptotic or necrotic cells affected DC maturation. We found that immature DCs efficiently phagocytose a variety of apoptotic and necrotic tumor cells. However, only exposure to the latter induces maturation. The mature DCs express high levels of the DC-restricted markers CD83 and lysosome-associated membrane glycoprotein (DC-LAMP) and the costimulatory molecules CD40 and CD86. Furthermore, they develop into powerful stimulators of both CD4(+) and CD8(+) T cells. Cross-presentation of antigens to CD8(+) T cells occurs after uptake of apoptotic cells. We demonstrate here that optimal cross-presentation of antigens from tumor cells requires two steps: phagocytosis of apoptotic cells by immature DCs, which provides antigenic peptides for major histocompatibility complex class I and class II presentation, and a maturation signal that is delivered by exposure to necrotic tumor cells, their supernatants, or standard maturation stimuli, e.g., monocyte-conditioned medium. Thus, DCs are able to distinguish two types of tumor cell death, with necrosis providing a control that is critical for the initiation of immunity.

Animals↗

PubMed1999

Improving cancer pain management using a performance improvement framework.

Pain is an important issue in quality of care and is increasingly cited as an outcome used to evaluate effectiveness of nursing care. Research indicates that nurses are not well prepared to care for patients with pain. Thus many patients are inadequately assessed and treated and consequently receive less than optimal pain management. The article describes the development, implementation, and evaluation of a pain education program designed to provide clinical nurses with the knowledge necessary to use appropriate pain management techniques. Program content stresses the use of a performance improvement framework for changing clinical practice in individual clinical settings.

Adult↗

PubMed1994

Control of cellular morphogenesis by the Ip12/Bem2 GTPase-activating protein: possible role of protein phosphorylation.

The IPL2 gene is known to be required for normal polarized cell growth in the budding yeast Saccharomyces cerevisiae. We now show that IPL2 is identical to the previously identified BEM2 gene. bem2 mutants are defective in bud site selection at 26 degrees C and localized cell surface growth and organization of the actin cytoskeleton at 37 degrees C. BEM2 encodes a protein with a COOH-terminal domain homologous to sequences found in several GTPase-activating proteins, including human Bcr. The GTPase-activating protein-domain from the Bem2 protein (Bem2p) or human Bcr can functionally substitute for Bem2p. The Rho1 and Rho2 GTPases are the likely in vivo targets of Bem2p because bem2 mutant phenotypes can be partially suppressed by increasing the gene dosage of RHO1 or RHO2. CDC55 encodes the putative regulatory B subunit of protein phosphatase 2A, and mutations in BEM2 have previously been identified as suppressors of the cdc55-1 mutation. We show here that mutations in the previously identified GRR1 gene can suppress bem2 mutations. grr1 and cdc55 mutants are both elongated in shape and cold-sensitive for growth, and cells lacking both GRR1 and CDC55 exhibit a synthetic lethal phenotype. bem2 mutant phenotypes also can be suppressed by the SSD1-vl (also known as SRK1) mutation, which was shown previously to suppress mutations in the protein phosphatase-encoding SIT4 gene. Cells lacking both BEM2 and SIT4 exhibit a synthetic lethal phenotype even in the presence of the SSD1-v1 suppressor. These genetic interactions together suggest that protein phosphorylation and dephosphorylation play an important role in the BEM2-mediated process of polarized cell growth.

Amino Acid Sequence↗

PubMed1994

Type 1 protein phosphatase acts in opposition to IpL1 protein kinase in regulating yeast chromosome segregation.

The IPL1 gene is required for high-fidelity chromosome segregation in the budding yeast Saccharomyces cerevisiae. Conditional ipl1ts mutants missegregate chromosomes severely at 37 degrees C. Here, we report that IPL1 encodes an essential putative protein kinase whose function is required during the later part of each cell cycle. At 26 degrees C, the permissive growth temperature, ipl1 mutant cells are defective in the recovery from a transient G2/M-phase arrest caused by the antimicrotubule drug nocodazole. In an effort to identify additional gene products that participate with the Ipl1 protein kinase in regulating chromosome segregation in yeast, a truncated version of the previously identified DIS2S1/GLC7 gene was isolated as a dosage-dependent suppressor of ipl1ts mutations. DIS2S1/GLC7 is predicted to encode a catalytic subunit (PP1C) of type 1 protein phosphatase. Overexpression of the full-length DIS2S1/GLC7 gene results in chromosome missegregation in wild-type cells and exacerbates the mutant phenotype in ipl1 cells. In addition, the glc7-1 mutation can partially suppress the ipl1-1 mutation. These results suggest that type 1 protein phosphatase acts in opposition to the Ipl1 protein kinase in vivo to ensure the high fidelity of chromosome segregation.

Amino Acid Sequence↗

PubMed1994

Regulation of yeast chromosome segregation by Ipl1 protein kinase and type 1 protein phosphatase.

Chromosome segregation is a complicated process that involves the coordinated functioning of a large number of cellular components. In this process, many proteins are activated and inactivated in a strict temporal order. While much progress has been made recently in the identification of structural components that are involved in chromosome segregation, relatively little is known about their regulation. We have investigated the chromosome segregation process in the budding yeast Saccharomyces cerevisiae. Our results indicate that this process absolutely requires a functional Ipl1 protein kinase. Upon inactivation of this protein kinase, yeast cells missegregate chromosomes severely and die within a single cell cycle. Furthermore, the inviability caused by a partial reduction in Ipl1 function can be rescued by perturbations that reduce type 1 protein phosphatase activity, thus suggesting that type 1 protein phosphatase acts in opposition to the Ipl1 protein kinase to insure the high fidelity of chromosome segregation in yeast cells. The purpose of this article is to describe some of our ongoing efforts to characterize Ipl1 and PP1 functions.

Aurora Kinases↗