Mode of action of the IgG inhibitor of erythropoiesis in transient erythroblastopenia of children

Twelve cases of transient erythroblastopenia of childhood (TEC) have been studied to evaluate their marrow cell erythropoiesis in vitro and the effect on it of their serum or IgG. The number of colony-forming units-erythroid (CFU-E) and burst-forming units-erythroid (BFU-E) in the bone marrow of nine cases was extremely variable and did not allow any conclusion regarding the pathogenesis of this anemia. An IgG inhibitor of growth of erythroid colonies or bursts was detected in 8/12 cases. This IgG inhibitor had no effect on the growth of granulocyte-macrophage colonies. Further studies on its mode of action indicated that the IgG did not have antierythropoietin antibody properties and did not affect the mature erythroblasts, as shown by a lack of inhibition of their responses to erythropoietin and by the lack of a cytotoxic effect on 59Fe-labeled erythroblasts. In four cases, preincubation studies demonstrated a direct effect of the IgG on the CFU-E, which was complement-mediated in three cases and complement- independent in one case. In two other cases, the IgG suppressed the growth of normal BFU-E only without affecting the growth of CFU-E. The IgG inhibitor was no longer present after the erythroblastopenia had remitted. These studies demonstrate that in the majority of cases of TEC, an IgG suppressor of erythropoiesis in vitro is present. Its mode of action is heterogeneous regarding its requirement for complement. Its target cells are the earlier or later erythroid progenitors, BFU-E or CFU-E, but not the differentiated erythroblasts.     

The significance of splenomegaly in 101 adults with acute lymphoblastic leukemia (ALL) at presentation and during remission

One-hundred-one adult patients with ALL were analyzed to determine the prognostic implications of splenomegaly occurring at any time during the course of their illness. The clinical status of the spleen at presentation was not found to be of major prognostic significance. Complete response rates, remission durations, and survivals did not differ between patients with and without splenomegaly at presentation. An enlarged spleen accompanied relapse in four patients. In six additional patients, splenomegaly was present during complete remission, and splenectomies performed in five of these patients revealed no evidence of leukemia to account for the splenomegaly. Splenectomy does not appear to be detrimental, as all five patients are currently in complete remission from 20 to 63 mo after splenectomy. Evidence implicating the spleen as a source of an antibody directed against autologous leukemia cells in one patient is reviewed.     

Cytogenetics of childhood T-cell leukemia

The karyotypes of 57 cases of childhood T-cell acute lymphoblastic leukemia (ALL) were analyzed to establish the cytogenetic profile in this disease. Three questions were of particular interest. Do the chromosomal changes in T-cell ALL preferentially affect bands where genes encoding the T-cell receptor for antigen (TCR) have been mapped? Do alterations involving the TCR gene regions appear with any notable frequency in B-progenitor ALL? Do chromosomal abnormalities in this disease relate to stage of T-cell ontogeny? A relatively high proportion of cases (65%) had a pseudodiploid karyotype at presentation, the majority (58%) characterized by a translocation. The overall frequency of translocations was 44%, comparable to that among all banded cases of ALL seen in our laboratory. Hypodiploidy and hyperdiploidy were exceedingly rare (only four of 57 cases); 16 cases (28%) had apparently normal karyotypes. In half the cases with a translocation (14 of 24), the breakpoints were in regions to which the alpha and beta chain TCR genes have been mapped. Chromosomal breakpoints that were consistently observed in the vicinity of TCR gene loci were 7q32-q36 (TCR beta chain; n = 8), 14q11-q13 (TCR alpha chain; n = 6); other frequent breakpoints were 9p13-pter (n = 8) and 6q15-qter (n = 9). Chromosomal alterations occurred near TCR gene loci significantly more often in T-cell cases than in a comparison group of 335 patients with B-cell precursor ALL (26% v 1.5%, P = .0001). Stage I thymocyte development (CD7+, CD2+, CD5+, CD1-, CD3-, CD4-, CD8-) was noted in 23 cases, stage II (CD7+, CD2+, CD5+, CD1+, CD3-, CD4 +/-, CD8 +/-) in 25 cases, and stage III (CD9+, CD2+, CD1-, CD5+, CD3+, and either CD4+ or CD8+) in nine cases. The only statistically significant associations between cytogenetic findings and T-cell ontogeny were a higher frequency of normal karyotypes in cases with stage I thymocytes, and of pseudodiploidy in stage II cases. There was no apparent relationship between particular translocations and level of thymocyte maturation. Our findings indicate that most children with T-cell ALL have pseudodiploid karyotypes, although a surprisingly high percentage lack demonstrable abnormal clones. Specific chromosomal changes do not appear to be related to discrete stages of T-cell ontogeny as defined in this study, but they occur preferentially in bands containing TCR genes.     

Effects of recombinant erythropoietin on the concentration and cycling status of human marrow hematopoietic progenitor cells in vivo

The concentration of human marrow progenitors CFU-E, BFU-E, CFU-GM, and CFU-Mk and the percentage of these progenitor cells in DNA synthesis were studied in nine patients with transfusion-dependent anemia of end- stage renal failure before and 2 weeks after treatment with human recombinant erythropoietin (Epo) at a dose of 150 to 300 U/kg intravenously three times per week. The concentration of CFU-E in the posttreatment marrow increased by a mean of 4.15-fold, BFU-E by 3.37- fold, CFU-GM by 1.86-fold, and CFU-Mk by 1.96-fold as compared with their respective concentrations in the pretreatment marrows. This increase in the concentrations of marrow progenitors was accompanied by almost a doubling of the percentage of these cells in DNA synthesis as assessed by the 3H-thymidine suicide technique. These observations demonstrate that at the progenitor cell level the human marrow responds to therapeutic doses of Epo as an organ rather than by a selective expansion of the erythroid cell line.     

Fatigue,anxiety, and quality of life in breast cancer patients compared to non-cancer controls: a nationwide longitudinal analysis

Breast Cancer Research and Treatment - Fatigue and anxiety are common and significant symptoms reported by cancer patients. Few studies have examined the trajectory of multidimensional fatigue and...     

Biological and catalytic potential of sustainable low and high valent metal-Schiff base sulfonate salicylidene pincer complexes

ONO-Pincer Schiff base salicylidene (HSaln ligand) complexes with VO²⁺, UO₂²⁺, MoO₂²⁺ and Mn²⁺ ions (MSaln complexes = VOSaln, UO₂Saln, MoO₂Saln and MnSaln, respectively) were synthesized and fully characterized by different physico-chemical tools. The VOSaln complex was further treated with 1,10-phenanthroline which afforded a new VO-complex (VOSaln-Ph). All complexes and their ligands, as eco-friendly reagents, were explored for their biological potential as antibacterial and antifungal agents. Reactivity of MSaln complexes against the tested pathogen strains exhibited a remarkable inhibitory effect compared to the coordinated ligand (HSaln) and applicable standard drugs. Moreover, the MSaln complex-DNA interaction was investigated by ultraviolet-visible spectroscopy, viscosity and gel electrophoresis techniques affording binding strengths in the order: UO₂Saln > MnSaln > MoO₂Saln > VOSaln-Ph > VOSaln. Additionally, the biological potential of the investigated compounds was further explored by molecular docking to illustrate the nature of the drug–DNA interactions. All MSaln complexes show respectable anti-proliferative potential as anticancer agents against selected human carcinoma cell lines. Aside from the biological activities these complexes (MSaln complexes) were also investigated for catalytic efficiency in the Suzuki–Miyaura cross-coupling system of phenylboronic acid with 2-bromopyridine in water, sustainably. The results indicated that the MnSaln catalyst performed well with high yield. The catalytic potential of MnSaln was compared in water, water–ionic liquid mixtures and ionic liquids.

ONO-Tridentate Schiff base complexes with VO²⁺, UO₂²⁺, MoO₂²⁺ and Mn²⁺ were synthesized and characterized. All the complexes were shown to be of potential use as anticancer agents against selected human carcinoma cell lines.     

Comparison of efficacy of three commercially available dentifrices on dentinal hypersensitivity: a randomized clinical trial

Background: Dentinal hypersensitivity has been defined as a short, sharp pain arising from exposed dentine as a result of various stimuli such as heat, cold, chemical, or osmotic, that cannot be ascribed to any other pathology. This study was conducted to assess the efficacy of three commercially available toothpastes in the reduction of dentinal hypersensitivity. Methods: A total of 149 subjects (72 males and 77 females; aged 20 to 60 years) were entered into the study and randomly divided into four groups: Group 1 – toothpaste containing 5% potassium nitrate; Group 2 – toothpaste containing 5% calcium sodium phosphosilicate with fused silica; Group 3 – toothpaste containing 3.85% amine fluoride; and Group 4 – a placebo toothpaste. After sensitivity scores for controlled air stimulus and cold water at baseline were recorded, subjects were given toothpastes and sensitivity scores were measured again at 2 weeks and 6 weeks. Results: All groups showed a reduction in sensitivity scores at 2 weeks and 6 weeks. The calcium sodium phosphosilicate group was found to be significantly better compared to the other groups at the end of 6 weeks. Conclusions: The calcium sodium phosphosilicate group showed a better reduction in the symptoms of dentinal hypersensitivity.     

Dendritic cells in childhood sepsis

Purpose

Our aim was to investigate the level and the maturation status of dendritic cells (DCs) in pediatric patients with sepsis and its relation to prognosis.

Materials and methods

The study included 16 children with sepsis, 24 children with complicated sepsis, and 40 healthy control children. The patients were investigated within 24 hours of intensive care unit admission and after 28 days. Flow cytometric detection of DCs was done.

Results

Within 24 hours, the levels of both plasmoid DCs and monocytoid DCs and the expression of CD86 and CD83 on DCs were significantly lower in patients than in controls, and the difference was marked in patients with complicated sepsis. The amount of CD86 and CD83 per cell was significantly lower in patients with complicated sepsis. The baseline numbers of monocytoid DCs and plasmoid DCs were higher in the survival patients than in nonsurvival patients. In addition, the expression of CD86 and CD83 on the entire DCs was significantly higher in the survival patients with sepsis.

Conclusion

Sepsis is associated with reduced level of DCs and decreases their maturation. The estimation of DCs number and maturation state may be used as prognostic makers of sepsis.