Umbilical cord blood transplantation--how, when and for whom?

In recent years, umbilical cord blood (UCB) has emerged as a feasible alternative source of hematopoietic progenitors (CD34+) for allogeneic stem cell transplantation, mainly in patients who lack HLA-matched marrow donors. Since the first case reported in 1998, more than 3500 patients have received UCB transplants for a variety of malignant and non-malignant diseases. The vast majority of recipients were children with an average weight of 20 kg; however, more than 500 UCB transplantations (UCBTs) have already been performed in adults. The "naive" nature of UCB lymphocytes also permits the use of HLA-mismatched grafts at 1-2 loci without higher risk for severe graft versus host disease (GvHD) relative to bone marrow transplantation (BMT) from a full matched unrelated donor. Furthermore, UCB is rich in primitive CD16(-)CD56++ NK cells, which possess impressive proliferative and cytotoxic capacities and can be induced to expand using IL-12 or IL-15, so as to mount a substantial graft versus leukemia (GvL) effect. The main disadvantage of UCB is the low stem cell yields, resulting in higher rates of graft failure as well as delayed time to engraftment compared to BMT. One rational approach to overcome this limitation involves ex vivo expansion of UCB derived hematopoietic precursors. In this review we tried to answer the question: UCBT how, when and for whom. This procedure is mostly applicable for children and especially those with indication for full allogeneic transplantation but who lack a matched sibling donor. Experimental approaches including ex vivo expansion of CB with cocktail of hematopoietic growth factors, with or without differentiation blocking agents, co-transplantation of haploidentical and CB cells or co-transfusion of CB and mesenchymal cells may enable successful UCBT in adults and probably will result in expanding the indication to solid tumors or autoimmune disorders.     

Effects of fibroblast growth factor-4 (k-FGF) on long-term cultures of human bone marrow cells

Fibroblast growth factor-4 (FGF-4), a highly mitogenic protein encoded by the k-fgf/hst oncogene, stimulates the growth of a variety of cells of mesenchymal and neuroectodermal origin. Addition of FGF-4 to human long-term bone marrow cultures increased both the cell density of the stromal layer and the number of hematopoietic colony forming cells in the cultures in a dose-dependent manner. Hematopoiesis in the stromal layer persisted for up to 8 months. Erythropoiesis was maintained for up to 4 weeks, but granulocytes were the predominant nonadherent cell type. Cultures treated with FGF had increased numbers of monocytes compared with control cultures and some CD14+, CD45+ monocytes could still be detected after 8 months of continuous culture. The addition of the growth factor increased the rate of growth of the stromal layer and appeared to delay its senescence. Subcultures made in the presence of FGF-4 had up to 10-fold increases in plating efficiency and grew as relatively uniform monolayers. These subcultures retained the capacity to support hematopoiesis for several months, while untreated subcultures, made without FGF-4, grew erratically and generally lost the capacity to support hematopoiesis within 4 to 6 weeks. The improved growth after subculture greatly enhanced the reliability of limit- dilution assays of multipotential hematopoietic stem cells that use stromal cell monolayers. The primary effect of FGF-4 appeared to be on the stromal cells of the long-term bone marrow cultures, but a direct effect on hematopoietic progenitors could not be ruled out.     

Assessment of the coagulation profile in hemato-oncological patients receiving ATG-based conditioning treatment for allogeneic stem cell transplantation

Antithymocyte globulin (ATG) is increasingly used in pre-allogeneic stem cell transplantation (allo-SCT) conditioning regimens to prevent graft rejection and graft-versus-host disease. However, ATG was also found to be associated with increased incidence of thrombosis during organ transplantation. In the present study, we tested the coagulation status of 21 patients with hematologic malignancies undergoing allo-SCT who received ATG-based (11 patients) or non-ATG-based (10) conditioning treatment. We assessed several thrombophilia markers as well as circulating total and endothelial microparticles (TMP/EMP) and soluble CD40 ligand (CD40L). No significant difference in the mean values of prothrombin time, partial thromboplastin time, fibrinogen, antithrombin, protein C, protein S, thrombin-antithrombin III complex, homocysteine levels, prevalence of genetic thrombophilia markers and levels of EMP, TMP or CD40L was observed between the ATG-treated and ATG-untreated patients, as well as before and after conditioning in each group separately. Platelet counts decreased significantly in ATG-treated patients; however, this decrease was not associated with clinical or laboratory evidence of disseminated intravascular coagulation. No patient developed thromboembolic event or veno-occlusive liver disease. Our results suggest that allo-SCT is not associated with increased hypercoagulability and addition of ATG to conditioning regimen has no significant procoagulant effect.     

Emergency pediatric radiology imaging trends for non-COVID-19-related illnesses through different stages of the pandemic

Emergency Radiology - To evaluate how the COVID-19 pandemic affected the imaging utilization patterns for non-COVID-19-related illness in a pediatric emergency department (ED). We retrospectively...     

Chemiluminescence response of polymorphonuclear leucocytes to serum-opsonized zymosan--a predictive parameter for infections and prognosis in multiple myeloma patients

Serum opsonization capability and phagocytosis by polymorphonuclear leucocytes (PMNL) were investigated in 37 patients with multiple myeloma (MM), 32 patients with chronic lymphocytic leukaemia (CLL), and 30 healthy controls. Opsonophagocytosis was assessed by measuring the chemiluminescence (CL) response of controls' and patients' PMNL to control- and patient-serum-opsonized zymosan particles. Control PMNL CL responses were significantly reduced both by MM and CLL sera. Normal sera restored the CL responses in MM patients, but only partially corrected the CL responses in CLL patients. Significant correlations were found between the CL responses in MM patients and four clinical parameters: clinical stage, presence of disease-related symptoms, incidence of bacterial infections, and outcome. The findings suggest a defect in MM and CLL sera opsonization ability which, at least in part, could account for the increased susceptibility to infections observed in these patients. Furthermore, the assessment of the CL response in MM patients is recommended as a simple and useful clinical tool for prediction of susceptibility to infection, and prognosis.     

Growth hormone heterogeneity in American plaice pituitaries: isolation, characterization, and partial amino acid sequence.

Growth hormones (GHs) have been isolated from pituitary glands of American plaice (Hippoglossoides platessoides), a marine flatfish, using affinity and gel filtration chromatography, followed by preparative polyacrylamide gel electrophoresis (PAGE). A bioassay based on serum triiodothyronine elevation in immature rainbow trout was used to monitor biological activity. These GHs originate from two molecular mass regions, 42K and less than 33K relative molecular mass (Mr), in their native state. The 42K Mr region yielded two forms of GH, which differ in terms of quantity and net charge as evidenced by native PAGE, a major variant with a relative mobility of (Rf) 0.22 and a lesser variant with Rf 0.28. The less than 33 Mr region has a single GH species with Rf 0.22. Upon sodium dodecyl sulfate-PAGE, without reduction, both GH variants from the 42K Mr region gave Mrs of 21K, while the GH from the less than 33K Mr region was 20K Mr, typical of monomeric vertebrate GHs. The proteins composing the 42K Mr region are proposed as GH dimers since they yield 21K Mr peptides. The less than 33K Mr region contains a GH monomer (20K Mr) in its native state. An amino-terminal amino acid sequence, identical for both the 42K and the 20K Mr Rf 0.22 forms, has good homology with other complete fish GH sequences near their carboxyl-terminal regions (between amino acids 130 and 196). The GH dimers (42K Mr) predominate in the plaice pituitary, contributing 93% of the total, of which 86% gives rise to the Rf 0.22 variant.     

Estrogen receptor mRNA expression patterns in the liver and ovary of female rainbow trout over a complete reproductive cycle

Estrogens are critical hormones involved in reproduction and need to bind to estrogen receptors in target organs for biological activity. Fishes have two distinct estrogen receptor subtypes, alpha (α) and beta (β), with variable combinations of additional isoforms of each subtype dependent on the history of genome duplication within a taxon. The comparative expression patterns of estrogen receptor isoforms during the female reproductive cycle will provide important insights into the unique function and importance of each. The purpose of this study was to measure the mRNAs for the four estrogen receptor isoforms (erα1, erα2, erβ1, erβ2) in the liver and ovary of adult, female rainbow trout over the course of an annual reproductive cycle. The expression of estrogen receptor mRNA isoforms was measured by quantitative real-time RT-PCR. Several reproductive indices (gonadosomatic index, maximum oocyte diameter, plasma estradiol-17β, plasma vitellogenin, and ovulation) were also quantified for comparison and used in a correlation analysis to examine any inter-relationships. Of the four isoforms, the expression of erα1 was highest in the liver, and had a significant positive correlation with liver erβ1 expression. Liver expression of erα2 mRNA was the lowest, but showed a significant positive correlation with maximum oocyte diameter in the ovary. The pattern of the erβ isoforms in liver was one of initially elevated mRNA expression followed by a gradual decrease as reproductive development proceeded. In the ovary the erβ1 isoform had the highest mRNA expression of all estrogen receptor isoforms, at the beginning of the reproductive cycle, but then decreased afterward. Both ovarian erβ isoforms had a significant positive correlation with one another. In contrast, erα2 mRNA expression showed a high maximum level in the ovary near the end of the cycle along with a significant positive correlation with plasma estradiol-17β levels; the highest gonadosomatic indices, maximum oocyte diameter, and vitellogenin levels occurred then too.