Myeloid antigens in childhood lymphoblastic leukemia:clinical data point to regulation of CD66c distinct from other myeloid antigens

Background  

Aberrant expression of myeloid antigens (MyAgs) on acute lymphoblastic leukemia (ALL) cells is a well-documented phenomenon, although its regulating mechanisms are unclear. MyAgs in ALL are interpreted e.g. as hallmarks of early differentiation stage and/or lineage indecisiveness. Granulocytic marker CD66c – Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is aberrantly expressed on ALL with strong correlation to genotype (negative in TEL/AML1 and MLL/AF4, positive in BCR/ABL and hyperdiploid cases).     

Chronobiological aspects of adult-onset Crohn disease

PURPOSE: To study the time course of Crohn disease and its signs. To compare the results with the world literature and draw conclusions for practice. BASIC PROCEDURES: Fifty-six patients were studied retrospectively: 31 males aged 19-48 years with disease duration 1-8 years, and 25 females aged 21-65 with disease duration 1-13 years. The disease was active (Crohn disease activity index > 150) in 25 patients and inactive in 31. Plasma levels of interleukin-6 (normal upper value 8 pg/ml) were investigated with radioimmunoassay. Bone mineral density was measured as the T-score (normal range between -1 and 0 standard deviations) in the forearm using dual-energy X-ray absorptiometry. The seasonality of births of the patients in relation to the total Slovak population and seasonality of severity of three important disease signs were examined with Halberg cosinor regression. The dependence of the signs on age and duration of disease was evaluated using quadratic regression. Results are presented as 95% confidence intervals (for means) and 95% tolerance intervals (for individuals). The level of statistical significance was set at alpha = 0.05. MAIN FINDINGS: Significant seasonality in births was found: decreased frequency in May-June and increased frequency in September-January. Significant spring elevation of interleukin-6 levels, accompanied by significant spring rise of the disease activity index and by decrease of bone density, is described. Among patients with active disease, interleukin-6 levels significantly increased up to the age of 41 years, whereas linear increase of disease activity during aging was on the borderline level of significance in the same subgroup. No significant age trend was encountered in T-score for either subgroup. The same was true for interleukin-6 and disease activity versus duration. Significant decrease in T-score paralleled disease duration up to seven years in the subgroup with active disease. PRINCIPAL CONCLUSIONS: The course of Crohn disease is influenced by time, including the seasons of the year. However, this does not find full agreement in the world literature, probably because of geographic, socioeconomic and epidemiologic differences, as well as varying approaches in method. In practice, regular monitoring of the time course is necessary in provision of appropriately timed treatment.     

Endotracheal colonization at birth is associated with a pathogen-dependent pro- and antiinflammatory cytokine response in ventilated preterm infants: a prospective cohort study

The possible association between mediators of inflammation such as cytokines and perinatal colonization of the respiratory tract remains unclear. This prospective cohort study evaluated endotracheal colonization in 141 ventilated preterm infants at birth. The relation with cytokine response in the airways and C-reactive protein (CRP) in umbilical blood was investigated. Of the 141 preterm infants enrolled in this study, 37 (26%) were colonized. In addition to traditional pathogens (61%), commensal species (26%) and Mycoplasmataceae (13%) were isolated. Both the pro-inflammatory cytokines IL-1 beta, IL-6, IL-8, and tumor necrosis factor (TNF)-alpha as well as the antiinflammatory IL-10 are increased in colonized patients in a dose-dependent manner, with the strongest response in neonates colonized with Gram-negative organisms. There was no antimicrobial IL-12p70 response in colonized infants. Commensal flora is associated with the same inflammatory response as traditional pathogens. Although the umbilical cord blood CRP level was significantly higher in neonates with endotracheal colonization, it was highest in those colonized with Gram-negative organisms but still close to normal limits. Microorganisms in the endotracheal fluid of ventilated preterm infants are associated with a pathogen-specific and dose-dependent cytokine response in the airways and systemic CRP response.     

Flow calorimetry--a useful tool for determination of immobilized cis-epoxysuccinate hydrolase activity from Nocardia tartaricans

Bacterial cells Nocardia tartaricans with cis-epoxysuccinate hydrolase activity were entrapped in hardened calcium pectate gel by a commercial high performance encapsulator. This enzyme (in a single step reaction with no formation of side products) was used to hydrolyze disodium cis-epoxysuccinate to a pure enantiomer--disodium L-(+)-tartrate. Activities of this enzyme were determined using flow calorimetry. The validity of this method was corroborated by HPLC and isotachophoresis. The immobilized biocatalyst has activity (75.8 U/mgdry) able to convert disodium cis-epoxysuccinate to disodium tartrate at 94% yield in 5.5h. Immobilization of N. tartaricans in hardened calcium pectate gel beads had a positive effect on the activity of cis-epoxysuccinate hydrolase, storage stability, yield, and time of bioconversion.     

Efficacy of praziquantel against Schistosoma haematobium infection in children

A study was performed to determine the efficacy of praziquantel (PZQ) against Schistosoma haematobium. Children (n = 592) infected with S. haematobium received either a single treatment with PZQ (40 mg/kg) or two or three treatments with PZQ at three-week intervals after the initial treatment and efficacy was monitored for nine weeks. Cure rates at three-weeks post-treatment were low (< 50%), suggesting either that worms are killed very slowly or, more likely, that eggs continue to be released from tissues after worm death. Interestingly, a single dose of PZQ showed high efficacy (cure rate > 83% and egg reduction rate > 98%) when assessed from six weeks post-treatment onward. There were no significant differences in cure rates or intensity of infection between the three cohorts at any point in the study, despite the different treatment regimens. Since children were in contact with transmission sites during the study period, the results suggest good efficacy of PZQ against all stages of S. haematobium, including the immature worms.     

Pharmacological hyperprolactinemia attenuates hydrocortisone-induced expression of CD11b on human CD8+ cells in vivo

OBJECTIVE: To study the short-term influences of pharmacologic hyperprolactinemia on hydrocortisone (HC)-induced effects on selected immune parameters. METHODS: A single dose of HC (40 mg per os) was administered to eleven healthy female volunteers 1 h after domperidone (10 mg per os) or placebo administration. Immune cell subsets and expression of adhesion molecules was assessed by flow cytometry at baseline and 4 and 6 h after HC administration. Intracellular staining of interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) production in CD4+ lymphocytes after phorbol myristate acetate and ionomycin stimulation was performed at the same time points. RESULTS: HC administration was followed by a significant increase in cortisol levels, numbers of leukocytes and granulocytes and the percentage of CD16+, CD19+, CD11a+, CD11a+CD8+, CD11b+ and CD11b+CD8+ cells. The number of lymphocytes and monocytes and the percentage of CD3+, CD4+, CD4+/CD8+ ratio, CD62L+, CD54+ and CD54+CD16+ cells decreased, while the percentage of CD8+ cells was unaffected. Domperidone administration resulted in a significant increase in prolactin (PRL) concentrations. During hyperprolactinemia, the HC-induced increase in CD11b+CD8+ cells was significantly (p < 0.05) attenuated at 4 h. HC-induced changes in other immune parameters remained unaffected. No significant changes in the intracellular production of IL-4 and IFN-gamma in CD4+ lymphocytes were observed after a single dose of HC alone or during hyperprolactinemia. CONCLUSIONS: This study shows an attenuated HC-induced increase in CD11b+CD8+ cells in the peripheral blood of healthy females during hyperprolactinemia. Our in vivo observations suggest that short-term interactions occur between PRL and glucocorticoids, affecting selected immune functions. Further studies are needed for confirmation of these results.     

Propofol in the management of postictal delirium with clozapine-electroconvulsive therapy combination

Postictal delirium is an acute confusional state occurring during the immediate postictal phase in patients receiving electroconvulsive therapy that is characterized by motor agitation, disorientation, clouded consciousness, repetitive stereotyped movements, and poor response to commands. A schizophrenic patient with severe and recurrent postictal delirium is described. The possible role of the clozapine-electroconvulsive therapy combination in the occurrence of postictal delirium is discussed. Several management strategies were tried, with various degrees of success. Propofol proved to be effective in preventing agitation when used as induction agent or when administered at seizure end. However, propofol could not prevent a delirious state when only administered after the first signs of motor restlessness had emerged.     

PP2A fulfills its promises as tumor suppressor: which subunits are important?

Reversible phosphorylation of proteins, catalyzed by kinases and phosphatases, is a key regulatory mechanism in the control of multiple cellular signal transduction pathways. Uncontrolled regulation by the altered phosphorylation state of the components of these pathways often leads to increased cell proliferation and cell transformation. Many viruses encode oncogenic proteins, required for their efficient viral replication, which deregulate the activity of host cell proteins. This might program cells to a malignant state, underlying the molecular mechanism of tumor formation and cancer development. Recent studies reveal a role for a specific form of protein phosphatase 2A (PP2A) in viral-induced cell transformation by interaction with the small t antigen (ST) of the DNA tumor simian virus 40 (SV40).