CD28 co-stimulation stabilizes the expression of the CD40 ligand on T cells

The ligand for CD40 (CD40L) is a protein which is expressed on CD4 T cells following their activation: CD40-CD40L interactions are absolutely required for the induction of T cell-dependent antibody responses, yet little is known about the mechanisms whereby CD40L+ primary T cells activate naive B cells, since the protein is only transiently expressed and is rapidly down-regulated following T cell-B cell contact. We show here, using a variety of assays, that co- stimulation of primary murine T cells via CD3 and CD28 stabilizes the expression of the CD40L protein. Firstly, T cells stimulated in this manner express higher levels of CD40L when activated in the presence of B cells, compared to CD3-activated T cells. Secondly, the CD40L expressed on CD28-co-stimulated T cells is more resistant to B cell- induced down-regulation. Finally, CD3/CD28-preactivated, rested T cells re-express higher levels of CD40L more rapidly following re-stimulation via CD3 than T cells preactivated via CD3 alone. CD3/CD28-preactivated T cells, but not CD3-activated cells, are competent to induce DNA synthesis in naive B cells, and this requires re-stimulation via CD3 and prolonged ligation of CD40. These data therefore reinforce the concept that naive T cells need to be activated initially by cognate interaction with B7-bearing antigen-presenting cells (such as dendritic cells), before becoming competent helper effector cells capable of driving B cells into proliferation via a CD40-dependent pathway.      

The inability of Streptococcus mutans and Lactobacillus acidophilus to form a biofilm in vitro on dentine pretreated with ozone

Background: The use of ozone therapy in the treatment of dental caries is equivocal. The aim of this study was to use an in vitro model to determine the effects of prior ozone application to dentine on biofilm formation and to measure any associated reduction in bacteria viability. Methods: Twenty dentine discs were bonded to the bases of 5 mL polycarbonate screw top vials. Ten dentine discs were infused with ozone for 40 seconds, 10 samples remained untreated as a control. The vials were filled with nutrient medium, sterilized and placed into the outflow from a continuous chemostat culture of Streptococcus mutans and Lactobacillus acidophilus for four weeks. At the conclusion of the experiment bacterial growth was monitored by taking optical density readings of the growth medium in each vial and the outer surface of the dentine specimens were examined by scanning electron microscopy as shown by SEM analysis. Results: Ozone infusion prevented biofilm formation on all the treated samples while there was substantial biofilm present on the control specimens. While the average optical density of the control specimens was almost twice that of the ozone infused dentine (0.710 for the control with a SD of 0.288 and 0.446 for the ozonated samples with a SD of 0.371), the results were not significant (p > 0.05). Conclusions: This preliminary study has shown that the infusion of ozone into non‐carious dentine prevented biofilm formation in vitro from S. mutans and L. acidophilus over a four‐week period. The possibility exists that ozone treatment may alter the surface wettability of dentine through reaction with organic constituents.     

Growth hormone therapy in pre-pubertal children with Noonan syndrome: first year growth response and comparison with Turner syndrome

We studied the growth-promoting effect of treatment with recombinant human growth hormone in 23 prepubertal children with Noonan syndrome, aged between 5. 4 and 14. 3 y, and all with a height < 1. 4 SD for Tanner standards. The growth response and skeletal maturation after 1 y of recombinant human growth hormone treatment (0. 15 U/kg/day given by daily injection) in the Noonan syndrome patients was compared with the auxological changes observed in a group of 17 girls with Turner syndrome with a comparable age and height deficit who were treated with recombinant human growth hormone in a similar way. During 1 y of treatment, the mean ± SD height velocity increased by 4. 0 ± 1. 6 cm/y in the Noonan syndrome group and by 3. 6 ± 1. 3 cm/y in the Turner syndrome group. Height SDS for chronological age in the Noonan syndrome group increased by 0. 53 ± 0. 46 ( p < 0. 001). In the Noonan syndrome patients the changes in height velocity were positively related to birthweight ( r = 0. 48, p < 0. 05). The changes in height velocity or height SDS were not related to the age, height deficit or a delay in bone age maturation at start of treatment. In neither the patients with Noonan syndrome nor Turner syndrome was an acceleration of bone maturation found. We conclude that treatment with recombinant human growth hormone in pre-pubertal NS patients induces an increase in height velocity and height SDS comparable to that observed in Turner syndrome girls.     

Glucocorticoid receptors in cord blood lymphocytes of healthy neonates and of preterms suffering from respiratory distress syndrome

We measured the number of glucocorticoid receptors (GR) in cord blood lymphocytes and the binding affinity (K_d) in 15 term and in 20 preterm babies. Thirteen preterms of the latter group received prenatal steroid treatment. Seven preterms developed neonatal respiratory distress syndrome (NRDS). The number of GR and the K_d were similar in the term and preterm (with and without NRDS) babies. The maximum thymidine incorporation into DNA of cord blood lymphocytes from all preterms, with or without NRDS was suppressed when compared to that from term babies or adults. This could partly be explained by the antenatal steroid treatment. Sensitivity (ID₅₀) of the lymphocytes for the inhibitory effect of dexamefhasone was the same in all groups. In this study on the number and function of GR in lymphocytes, we were unable to find a relation between the functionality of the GR and the development of NRDS.     

Anomalous ABO inheritance explained by ovum transplantation

BACKGROUND: Modern fertilization techniques can lead to unexpected ABO phenotypes in newborn infants and can raise questions as to maternity, paternity, and infant misidentification. Ovum transplantation can result in an infant with an ABO phenotype that is unexpected, given the birth mother's ABO type. STUDY DESIGN AND METHODS: A group AB, Rh- positive female infant was born to a group O, Rh-positive woman as a result of ovum transplantation. The case report is provided. RESULTS: The birth mother typed group O, Rh-positive both before and after delivery. The infant typed group AB, Rh-positive on cord blood and heelstick specimens. CONCLUSION: Ovum transplantation can result in newborns whose ABO phenotypes are unexpected, in relation to the birth mother's ABO type. To ensure patient privacy, such fertilization techniques may not be clearly documented in the delivery room chart. A complete obstetric history helps prevent repeat phlebotomies, expensive and unnecessary typing studies, and concern of the clinical staff with possible sample or infant misidentification.     

A possible autocrine role for interleukin-6 in two lymphoma cell lines

Interleukin-6 (IL-6) is a growth factor with diverse biologic activity. Originally described as a T-cell product that enhances immunoglobulin (Ig) secretion in antigen-stimulated B cells, it also affects the growth of T cells, plasmacytomas, hybridomas, and hematopoietic stem cells. We report the expression and secretion of IL-6 by two lymphoma cell lines, OCI-LY3 and OCI-LY12. Addition of recombinant IL-6 stimulated their growth, whereas addition of polyclonal anti- recombinant IL-6 (anti-rIL-6) had a marked inhibitory effect on proliferation. These results suggest an autocrine role for IL-6 in the growth of these lymphoma cells in culture.     

Cytokines in inflammatory malignant fibrous histiocytoma presenting with leukemoid reaction

Inflammatory malignant fibrous histiocytomas (IMFH) are rare tumors and are frequently associated with leukocytosis. In rare cases, leukemoid reactions were attributed to tumor production of unidentified hematopoietic factors. In this study, we used immunohistochemical techniques to show cytokine immunoreactivity in the malignant cells of two cases of IMFH presenting with leukemoid reactions and compared them with two malignant fibrous histocytomas, noninflammatory type. All four tumors stained positively for stem cell factor (SCF), granulocyte colony-stimulating factor (G-CSF), interleukin-2 (IL-2), IL-4, IL-5, interferon-alpha (IFN-alpha), and insulin-like growth factor-I. Other cytokines detected only in the two IMFH included IL-6, IL-7, IL-8, IFN- gamma, and keratinocyte growth factor. Granulocyte-macrophage-CSF, IL- 3, and transforming growth factor-beta staining was present in one of the two IMFH tumors and was not present in the noninflammatory tumors. The immunohistochemical staining was localized to the malignant cells, suggesting deregulated cytokine expression consistent with their monocytic/histocytic origin. Expression of certain cytokines in the IMFH may account for the local inflammatory infiltrate, tumor fibrosis, and the aggressive nature of the malignant cells. We also detected elevated serum levels of SCF, G-CSF, IL-6, and tumor necrosis factor in one or both of the IMFH patients. These latter observations may explain the bone marrow hypercellularity and other paraneoplastic symptoms, including fever, malaise, and weight loss, observed in both patients. Different cytokines present in the two IMFH tumors appear to be responsible for the eosinophilic leukemoid reaction observed in one case and for the granulocytic leukemoid reaction observed in the other patient. They may also be responsible for expansion of the tumor-cell population, fibroblast proliferation, and enhanced secretion of extracellular collagen.     

Metformin improves performance in high‐intensity exercise,but not anaerobic capacity in healthy male subjects

The aim of this study was to determine the ergogenic effects of metformin in high‐intensity exercise, as well as its effects on anaerobic capacity, in healthy and physically active men. Ten subjects (mean (± standard deviation) maximal oxygen uptake (_2max) 38.6 ± 4.5 mL/kg per min) performed the following tests in a cycle ergometer: (i) an incremental test; (ii) six submaximal constant workload tests at 40%–90% (_2max); and (iii) two supramaximal tests (110% (_2max). Metformin (500 mg) or placebo was ingested 60 min before the supramaximal test. There were no significant differences between the placebo and metformin groups in terms of maximum accumulated oxygen deficit (2.8 ± 0.6 vs 3.0 ± 0.8 L, respectively; P = 0.08), lactate concentrations (7.8 ± 2.6 vs 7.5 ± 3.0 mmol/L, respectively; P = 0.75) or O₂ consumed in either the last 30 s of exercise (40.4 ± 4.4 vs 39.9 ± 4.0 mL/kg per min, respectively; P = 0.35) or the first 110 s of exercise (29.0 ± 2.5 vs 29.5 ± 3.0 mL/kg per min, respectively; P = 0.42). Time to exhaustion was significantly higher after metformin than placebo ingestion (191 ± 33 vs 167 ± 32 s, respectively; P = 0.001). The fast component of recovery was higher in the metformin than placebo group (12.71 vs 12.18 mL/kg per min, respectively; P = 0.025). Metformin improved performance and anaerobic alactic contribution during high‐intensity exercise, but had no effect on overall anaerobic capacity in healthy subjects.