Immunostimulatory DNA: sequence-dependent production of potentially harmful or useful cytokines

Certain bacterial immunostimulatory (i.s.) DNA sequences containing unmethylated CpG motifs stimulate antigen-presenting cells (APC) to express a full complement of costimulatory molecules and to produce cytokines including interleukin (IL)-12 and tumor necrosis factor (TNF)-alpha. While IL-12 is key to their T helper cell (Th)1-promoting adjuvant activity, secretion of toxic levels of TNF-alpha is harmful in that it promotes toxic shock. Given the beneficial as well as harmful consequences of i.s. DNA, we investigated the possibility of identifying DNA sequences, i.e. CpG oligodeoxynucleotides (ODN) which differentially activate IL-12 versus TNF-alpha cytokine production in APC. Here, we describe an i.s. DNA sequence with these characteristics. While its potential to induce IL-12 is preserved, its ability to trigger TNF-alpha release is strongly curtailed both in vitro and in vivo. I.s. DNA could be segregated into lethal and non-lethal in a mouse toxic shock model. The non-toxic i.s. DNA was useful as an adjuvant, thus allowing cytotoxic T cell responses to the soluble protein ovalbumin and conferring a resistant Th 1 phenotype to BALB/c mice lethally infected with Leishmania major. This i.s. CpG motif may thus be prototypic for a useful immunostimulating DNA sequence that lacks harmful side effects.     

Mutagenic and antimutagenic activities of human whole blood, plasma and albumin

The seeds of Crepis capillaris were used to examine the mutagenic und antimutagenic properties of human whole blood, plasma, serum albumin and gamma-globulin by recording chromosomal and chromatid aberrations. The antimutagenic activity was determined by preliminary, simultaneous, and subsequent biosubstrate treatments of the seeds. The whole and twice-diluted blood, as well as plasma, induced aberrations exceeding the level of self-arbitrary mutagenesis by 3.7-5.3 and 2.6-3.1 times, respectively. When the blood was diluted to its 20% concentration, the antimutagenic efficiency of biological fluids was recorded. Human serum albumin and gamma-globulin were found to have an antimutagenic effect. In the dilutions having no antimutagenic effect, blood, plasma, and albumin showed their ability to be effectively decrease the level of induced aberrations.     

The effects of treatment with PIXY321 (GM-CSF/IL-3 fusion protein) on human polymorphonuclear leukocyte function

During a phase I trial of the genetically engineered hematopoietic growth factor PIXY321 (granulocyte-macrophage colony-stimulating factor/interleukin-3 [IL-3] fusion protein), we examined the effects of PIXY321 treatment on human polymorphonuclear leukocyte (PMN) locomotive, respiratory burst, and phagocytic responses. PIXY321 treatment was associated with transient suppression of both unstimulated locomotion and chemotaxis responses to multiple stimuli, as well as significant transient enhancement of formyl peptide-stimulated H2O2 production. No effects on opsonic phagocytosis of Staphylococcus aureus were observed. In vitro exposure of control PMN to PIXY321 resulted in suppression of unstimulated locomotion/chemotaxis and enhancement of formyl peptide-stimulated H2O2 production but had no effects on phagocytosis. When patient cells were exposed in vitro to PIXY321 during treatment, suppression of chemotaxis and enhancement of H2O2 production were observed before PIXY321 treatment, but these effects diminished during treatment. The in vivo and in vitro exposure effects of PIXY321 treatment on PMN function are similar to those of the parent molecule, granulocyte-macrophage colony-stimulating factor (GM-CSF).     

Laboratory millimeter wave measurements of atmospheric aerosols

Measurements made in an untuned resonator by Fourier Transform Spectroscopy of atmospheric aerosols are explained by a pumped phonon model due to Fröhlich.     

Detection of human papillomavirus in routinely processed biopsy specimens from laryngeal papillomas: evaluation of reproducibility of polymerase chain reaction and DNA in situ hybridization procedures

The frequency of human papillomavirus (HPV) in laryngeal papillomas varies largely among different studies. DNA in situ hybridization (ISH) has been the most widely used method for detection of HPV. The aim of this study was to compare the reproducibility and sensitivity of ISH with polymerase chain reaction (PCR) in 35 specimens of laryngeal papillomas routinely fixed in buffered or unbuffered formalin. Out of 12 specimens fixed in buffered formalin, 10 were positive for HPV 6/11 using ISH. The procedure was repeated three times and three specimens were positive only twice. Nine biopsies were positive for HPV using PCR with consensus primers (My 09/11) on dewaxed tissue without extracting DNA. In three repeated PCRs, the results were inconsistent in three samples. After DNA extraction, all 12 samples were positive with PCR. Of the 23 specimens fixed in unbuffered formalin, 14 were HPV-positive with ISH, while only one was positive with PCR. We concluded that PCR with My 09/11 consensus primers is a highly sensitive method for detection of HPV in laryngeal papillomas fixed in buffered formalin, but useless for samples fixed in unbuffered formalin. When DNA was extracted from the former type of fixed tissue, the results were highly reproducible. In contrast to PCR, ISH appeared to be less influenced by fixation procedure, but it was not as reproducible and sensitive as PCR. Negative results did not necessarily mean absence of HPV.     

Accelerating entry into supported employment for persons with severe psychiatric disabilities.

Tested the hypothesis that Ss with severe mental illnesses would achieve better vocational outcomes with an accelerated approach to supported employment (AASE), as compared to gradual approaches (GA) with prevocational training. 86 Ss (mean age 35.1 yrs) with a diagnosis of a serious mental illness, were randomly assigned to either the AASE, or the GA, which included a minimum of 4 mo prevocational training. Data were obtained on indicators of vocational outcomes over 2 yrs, and for a limited number of Ss (n=36), during the 4th yr of inception into the program. Initially, only 5% of Ss preferred prevocational training. After 1 yr, AASE Ss showed better outcomes for a range of indicators, including achievement of competitive employment, duration of employment and mean earnings. During the 4th yr, 59% of these Ss were competitively employed, as compared to only 6% of GA Ss. Rehabilitation is more effective using AASE than GA. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ultrastructural studies of the ileum neobladder

Of 101 women, 15-50 years of age, presenting with vaginal discharge, 34 had bacterial vaginosis and were randomly assigned to a seven-day course of oral treatment with either erythromycin (0.5 g b.i.d.) or metronidazole (0.4 g b.i.d.) in a single-blind, cross-over study. Treatment failure (> or = three clinical signs of bacterial vaginosis) occurred in 13 (81%) of 16 patients given erythromycin, as compared with three (17%) of 18 women treated with metronidazole (p < 0.001). Persistence of Gardnerella vaginalis, Mobiluncus species and/or Mycoplasma hominis was found in 14 of 16 patients treated with erythromycin, and in four of 16 patients treated with metronidazole. Treatment with metronidazole was successful (< or = two clinical signs of bacterial vaginosis) in eight of 10 cases of erythromycin treatment failure. Neither of two cases of metronidazole treatment failure was cured with erythromycin. At three-month follow-up of 31 women, persistence or recurrence of bacterial vaginosis was diagnosed in 11 cases (36%).     

Camcorders

The author explains from an engineering standpoint, how some of the camcorder components work. He discusses the solid-state image sensor, the photodetector, scanning, the shutter frame rate, optics, the recording mechanism, the viewfinder, special effects, and automatic features. Motion detection, discrimination, and compensation are also covered. Recommendations as to which features are most useful are made