Assessment of traffic noise levels in urban areas using different soft computing techniques.

Available traffic noise prediction models are usually based on regression analysis of experimental data, and this paper presents the application of soft computing techniques in traffic noise prediction. Two mathematical models are proposed and their predictions are compared to data collected by traffic noise monitoring in urban areas, as well as to predictions of commonly used traffic noise models. The results show that application of evolutionary algorithms and neural networks may improve process of development, as well as accuracy of traffic noise prediction.

Systemic lupus erythematosus complicated with pulmonary hemorrhage in a 17-year-old female.

Pulmonary hemorrhage is a rare and life-threatening complication of systemic lupus erythematosus. In this report, we described a 17-year-old female with pulmonary hemorrhage as an initial manifestation of systemic lupus erythematosus, along with lupus nephritis and central nervous system lupus. High doses of corticosteroids and pulse cyclophosphamide therapy resulted in rapid improvement of respiratory function in our patient.

Prolonging microtubule dysruption enhances the immunogenicity of chronic lymphocytic leukaemia cells.

Cytotoxic chemotherapies do not usually mediate the expression of an immunogenic gene programme in tumours, despite activating many of the signalling pathways employed by highly immunogenic cells. Concomitant use of agents that modulate and complement stress-signalling pathways activated by chemotherapeutic agents may then enhance the immunogenicity of cancer cells, increase their susceptibility to T cell-mediated controls and lead to higher clinical remission rates. Consistent with this hypothesis, the microtubule inhibitor, vincristine, caused chronic lymphocytic leukaemia (CLL) cells to die rapidly, without increasing their immunogenicity. Protein kinase C (PKC) agonists (such as bryostatin) delayed the death of vincristine-treated CLL cells and made them highly immunogenic, with increased stimulatory abilities in mixed lymphocyte responses, production of proinflammatory cytokines, expression of co-stimulatory molecules and activation of c-Jun N-terminal kinase (JNK), p38 and nuclear factor kappa B (NF-kappaB) signalling pathways. This phenotype was similar to the result of activating CLL cells through Toll-like receptors (TLRs), which communicate 'danger' signals from infectious pathogens. Use of PKC agonists and microtubule inhibitors to mimic TLR-signalling, and increase the immunogenicity of CLL cells, has implications for the design of chemo-immunotherapeutic strategies.

Immunomodulatory effects of Toll-like receptor-7 activation on chronic lymphocytic leukemia cells.

Weak immunogenicity of chronic lymphocytic leukemia (CLL) cells may contribute to disease progression and inhibit effective immunotherapy. Accordingly, agents that enhance the immunogenicity of CLL cells may be useful in immunotherapeutic approaches to this disease. Since Toll-like receptors (TLRs) are major regulators of innate immunity and initiation of adaptive immunity, we studied the effects of viral pathogen associated molecular pattern agonists (that are recognized by TLRs) on the costimulatory phenotype and function of CLL cells. CLL cells (especially those with high endogenous expression of CD38) responded to TLR7-activating imidazoquinolines and guanosine analogs by increasing costimulatory molecule expression, producing inflammatory cytokines, and becoming more sensitive to killing by cytotoxic effectors. Additional activation of protein kinase C pathways increased the ability to stimulate T-cell proliferation, blocked phosphorylation of the transcription factor, signal transducer and activator of transcription (STAT)3, and resulted in the acquisition of a dendritic cell surface phenotype by TLR7-activated CLL cells. Normal B cells also responded to TLR7 activation by increasing costimulatory molecule expression and cytokine production. These findings suggest a potential role for TLR7 agonists in CLL immunotherapy.

Aberrant O-GlcNAcylation characterizes chronic lymphocytic leukemia.

O-linked N-Acetylglucosamine (O-GlcNAc) post-translational modifications originate from the activity of the hexosamine pathway, and are known to affect intracellular signaling processes. As aberrant responses to microenvironmental signals are a feature of chronic lymphocytic leukemia (CLL), O-GlcNAcylated protein levels were measured in primary CLL cells. In contrast to normal circulating and tonsillar B cells, CLL cells expressed high levels of O-GlcNAcylated proteins, including p53, c-myc and Akt. O-GlcNAcylation in CLL cells increased following activation with cytokines and through toll-like receptors (TLRs), or after loading with hexosamine pathway substrates. However, high baseline O-GlcNAc levels were associated with impaired signaling responses to TLR agonists, chemotherapeutic agents, B cell receptor crosslinking and mitogens. Indolent and aggressive clinical behavior of CLL cells were found to correlate with higher and lower O-GlcNAc levels, respectively. These findings suggest that intracellular O-GlcNAcylation is associated with the pathogenesis of CLL, which could potentially have therapeutic implications.

[Intravenous immunoglobulin in the treatment of infections in children with acute leukemias]. / Primena intravenskog imunoglobulina u terapiji infekcija dece s akutnim leukemijama.

Infections are a common cause of complications in the course of applying highly aggressive combined cytotoxic therapy in children suffering from acute leukemias (ALL and ANLL). The effect of adjuvant therapy of intravenous immunoglobulins (IVIG) was investigated in cases of infections of children with ALL and ANLL (24 with IVIG and 24 without this therapy) according to the system of matched pairs. The polyvalent functionally intact monomeric i.v. immunoglobulin "Endobulin" Immuno, 100 mg/kg was applied in infections--febrile episodes combined, if possible, with an aimed antibiotic therapy. It was established that children with the intravenous immunoglobulin therapy had had statistically significantly less febrile episodes (p < 0.01), as well as less febrile days (p < 0.05). Although the acquired results speak in favor of this therapeutic possibility when applying this supportive therapy which is getting more and more important, authors made a conclusion that the final estimate of the value of this therapy remains open and requires further investigations.

[Personal experience in the immunomodulation of immunothrombocytopenic purpura in children using high doses of i.v. immunoglobulin]. / Nasa iskustva u imunomodulaciji kod imunotrombocitopenijske purpure u dece primenom visokih doza i.v. imunoglobulina.

Twenty-three child patients with immunothrombocytopenic purpura ITP were treated with high doses of immunoglobulins for intravenous application. The dose applied was 400 mg/kg during five consecutive days. The immunological status of all patients was determined previously, and beside the normal values of the IgG serum, a deficit of the IgG2 subclass was discovered in 12 patients. The therapy effect was satisfactory in 19 patients, and 4 had an absence of a satisfactory response to therapy. There was an interesting observation that all patients with a good response to therapy had a deficit of the IgG2 subclass, while with all the other patients without a satisfactory response to therapy the, IgG2 subclass had normal values. On the basis of the results observed it can be concluded that i.v. immunoglobin therapy in high doses has it's place in the immunothrombocytopenia treatment of children, and especially of patients with an IgG2 subclass deficit.