Severity of respiratory syncytial virus disease related to type and genotype of virus and to cytokine values in nasopharyngeal secretions

BACKGROUND: Investigations concerning the severity of respiratory syncytial virus (RSV) disease as related to (1) RSV type and genotype determined respectively by PCR and restriction enzyme analysis and (2) interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) values in samples of nasopharyngeal secretion (NPS) have not been previously reported. METHODS: We prospectively studied 105 RSV infections in the lower respiratory tract of infants and young children admitted to a pediatric department in Copenhagen during three winter seasons, 1993, 1994 and 1995. RSV strains were typed and genotyped, respectively, by PCR and nucleic acid restriction analysis and correlated to the severity of the disease. The ratio IL-6:TNF-alpha, determined from IL-6- and TNF-alpha values in samples of NPS, was related to the severity of the disease. Concentrations of IL-6 and of TNF-alpha were determined in serum samples taken during 5 weeks after the onset of illness. RESULTS: Type B infections produced more severe disease than did type A infections, as assessed on the length of the hospital stay, use of respiratory support and the presence of an infiltrate on a chest radiograph. This difference was age-related. It was observed in infants 0 to 5 months old, but not in older age groups. Type B genotype B1122 produced more severe disease than type A genotype A2311 in infants 0 to 11 months old. Increased serum concentrations of IL-6 and TNF-alpha were detected in samples taken 1 to 2 days after the onset of illness. Whereas TNF-alpha serum concentrations remained high, IL-6 serum concentrations decreased during the following 3 to 4 weeks. The IL-6:TNF-alpha ratio in samples of NPS was related to the severity of the disease. A high ratio was related to a low severity. CONCLUSIONS: The severity of disease in patients admitted with acute RSV infections can be correlated to the RSV type as determined by PCR, to the RSV genotype as determined by nucleic acid restriction analysis and to the ratio IL-6:TNF-alpha in NPS.     

Hemodynamic effects of the somatostatin analog lanreotide in humans: placebo-controlled, cross-over dose-ranging Echo-Doppler study

Fas is expressed in various cells and transduces the cell death signal. p21 is a mediator of p53-dependent G1 arrest associated with deoxyribonucleic acid (DNA) damage. The upregulation of p53 and p21 associated with DNA damage in idiopathic pulmonary fibrosis has been described previously. In this study, p53, p21, and Fas expression and DNA damage were examined in interstitial pneumonia associated with collagen vascular diseases (CVD-IP). DNA damage was assessed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end-labelling (TUNEL) and p53, p21 and Fas proteins were detected by immunohistochemistry in 13 cases of CVD-IP, 13 of sarcoidosis, seven of hypersensitivity pneumonitis (HP) and eight control patients with normal lung parenchyma. TUNEL-positive signals were found in bronchiolar or alveolar epithelial cells in 11 of 13 (85%) specimens of CVD-IP, but not in sarcoidosis, HP or controls, except for a case of chronic HP with pulmonary fibrosis. p53, p21 and Fas were detected in bronchiolar or alveolar epithelial cells in nine (69%), 10 (77%) and 12 (92%) of 13 specimens of CVD-IP, respectively, but not in sarcoidosis, HP or controls, except for a case of chronic HP. These results suggest that the upregulation of p53, p21 and Fas in bronchiolar and alveolar epithelial cells associated with deoxyribonucleic acid damage may participate in the process of pulmonary fibrosis in interstitial pneumonia associated with collagen vascular diseases and chronic hypersensitivity pneumonitis.     

Urocanic acid isomers in patients with basal cell carcinoma and cutaneous malignant melanoma

Urocanic acid (UCA) is a major chromophore for ultraviolet (UV) radiation in the skin. On UV exposure, the naturally occurring trans-isomer converts to the cis-isomer in a dose-dependent manner. Accumulating evidence indicates that cis-UCA acts as an initiator of the UV-induced suppression of certain skin immune functions. This immunomodulation is recognized as an important factor in the development of skin cancer. In this study, pigmentation and UCA isomers were measured in 29 patients with previous basal cell carcinoma (BCC), 23 patients with previous cutaneous malignant melanoma (MM), and 32 healthy controls. Measurements were performed on UV-exposed (forehead, upper back) and UV non-exposed (buttock) skin. No significant differences in pigmentation percentage, total UCA concentration, relative (%) or absolute (nmol/cm2) cis-UCA concentration were observed between the groups in any of the body sites studied. The net production of cis-UCA after irradiation with a single test UV dose was evaluated. The relative production of cis-UCA following irradiation was significantly higher in both cancer groups when compared with the control group, while no significant difference was found between the BCC and the MM patients.     

Distinguishing small molecular mass differences of proteins by mass spectrometry

This study was undertaken to determine if acidic or basic fibroblast growth factor (FGF1 or FGF2) or vascular endothelial growth factor (VEGF) alters the radiation response of small bowel after total-body irradiation (TBI). Female C3H mice were treated with various doses of angiogenic growth factor administered intravenously 24 h before or 1 h after TBI. Radiation doses ranged from 7 to 18 Gy. End points measured were the number of crypts in three portions of the small bowel, the frequency of apoptosis of crypt cells at various times after TBI, and the LD50/30 (bone marrow syndrome) and LD50/6 (GI syndrome). Fibroblast growth factors alone, without TBI, decreased the number of crypts per circumference significantly. Among the factors tested, FGF2 caused the greatest decline in baseline crypt number. Despite this decrease in the baseline crypt number, after irradiation the number of surviving crypts was greater in animals treated with growth factor. The greatest radioprotection occurred at intermediate doses of growth factor (6 to 18 pg/mouse). Mice treated with FGF1 and FGF2 had crypt survival curves with a slope that was more shallow than that for saline-treated animals, indicating radiation resistance of crypt stem cells in FGF-treated mice. The LD50/6 was increased by approximately 10% for all treatments with angiogenic growth factors, whether given before or after TBI. Apoptosis of crypt cells was maximum at 4 to 8 h after TBI. The cumulative apoptosis was decreased significantly in animals treated with angiogenic growth factors, and the greatest protection against apoptosis was seen in animals treated with FGF2 prior to TBI. All three angiogenic growth factors tested were radioprotective in small bowel whether given 24 h before or 1 h after irradiation. The mechanism of protection is unlikely to involve proliferation of crypt stem cells, but probably does involve prevention of radiation-induced apoptosis or enhanced repair of DNA damage of crypt cells.     

Isocyanates,aminoisocyanates and amines from fires—a screening of common materials found in buildings

Isocyanates, aminoisocyanates and amines were quantified from the combustion of 24 different materials or products typically found in buildings. Small‐scale combustion experiments were conducted in the cone calorimeter, where generally well‐ventilated combustion conditions are attained. Measurements were further made in two different full‐scale experiments. Isocyanates and amino‐compounds were sampled using an impinger‐filter sampling system with a reagent solution of di‐n‐butylamine in toluene. Filter and impinger solution were analysed separately using LC‐MS technique. Further the particulate distribution in the smoke gases was determined by impactor technique, and selected gaseous compounds quantified by FTIR. It was found in the small‐scale that isocyanates were produced from the majority of the materials tested. The highest concentration was found for glass wool insulation, and further high concentrations were found for PUR products, particleboard, nitrile rubber and melamine. Lower concentrations were found for wood and cable‐products. Amino‐isocyanates and amines were generally found from PUR products only. The distribution of isocyanates between the particulate‐ and fluid phases varied for the different materials and a tendency to enrichment of particles was seen for some of the materials. Further, when comparing the potential health hazard between isocyanates and other major fire gases (based on NIOSH IDLH‐values) it was found that isocyanates in several cases represented the greatest hazard. Copyright © 2003 John Wiley & Sons, Ltd.     

Dimethylarsine: Pyrolysis mechanisms and use for OMVPE growth

The pyrolysis mechanisms of dimethylarsine (DMAsH) have been studied mass spectrometrically in an atmospheric pressure flow tube reactor. In either the D₂ or He ambient, DMAsH will be converted to trimethylarsine (TMAs) at temperatures of 400–500° via a homogeneous CH₃ radical chain reaction. Supplemental CH₃ radicals, produced from azomethane ((CH₃)₂N₂) pyrolysis, have resulted in a significant increase in the pyrolysis rate for DMAsH. As temperature is increased beyond 500°, the product TMAs will decompose due to hydrogenolysis in D₂ and homolysis in He. At a GaAs surface, DMAsH pyrolyzes heterogeneously. The pyrolysis rate is further accelerated by the addition of trimethylgallium (TMGa). DMAsH has also been combined with TMGa to grow GaAs layers. The as-grown epilayers, at 1 atm and substrate temperatures of 570–720°, are allp-type with the net hole concentration dependent on the carrier gas. The use of N₂ leads to a higher concentration as compared to that in H₂. Photoluminescence spectra have indicated the acceptor to be carbon. A mechanism is developed to interpret these results based on the pyrolysis reactions determined from the kinetic studies.     

Three isoflurane preparations from various manufacturers. A comparison of isoflurane concentrations in fresh gas after vaporization with a Drager vaporizer type 19.3

OBJECTIVES: The purpose of this study was to check the precision of the Dr?ger vaporizer model 19.3 when filled with three different preparations of isoflurane. METHODS: Six Dr?ger vaporizers model 19.3 calibrated with forene were filled with forene (Abbott), isoflurane (Lilly) and isoflurane (Pharmacia); gas output was measured by infrared absorption (Irina, Dr?ger) at vaporizer settings of 0.2, 0.4, 0.6, 0.8, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0 and 5.0 vol%, starting with a fresh gas flow of 2 1/min followed by 4, 6 and 12 1/min. Thus each of the three isoflurane preparations was checked in six different vaporizers and with four different fresh gas flows. RESULTS: Within the concentration range used in clinical practice there was no significant difference in the delivery of the three isoflurane preparations. Each of the six vaporizers produced a controllable and predictable concentration of the three preparations. CONCLUSION: Vaporizers of Dr?ger type 19.n calibrated with forene deliver the same predictable concentration of the volatile anaesthetic when filled with isoflurane from Lilly or isoflurane from Pharmacia instead of forene and may be used without impairment in patient safety. In addition, no specific calibration with one of the new isoflurane preparations is required.     

Nematode-trapping fungi in biological control of Dictyocaulus viviparus

A protocol is described for coupling of carrier-free iodine to protein sulfhydryl groups via fluorescein maleimide. 125I is first coupled to fluorescein maleimide in the presence of chloramine T. Iodination is stopped with sodium thiosulfate, and the iodine-substituted fluorescein maleimide is reacted with free cysteines of the protein. Excess label is then removed by gel-permeation chromatography. The procedure avoids exposition of the protein to oxidative conditions and does not require purification of the labeled carrier reagent. Suitability of the method for a given protein can be evaluated spectrophotometrically without employing radioactivity. It can be applied under denaturing conditions and may be particularly useful with mutant proteins carrying engineered single cysteine residues at sites that are not functionally critical.     

Recombinant human growth-regulated oncogene-alpha induces T lymphocyte chemotaxis. A process regulated via IL-8 receptors by IFN-gamma, TNF-alpha, IL-4, IL-10, and IL-13

The human cytokine growth-regulated oncogene (GRO)-alpha is a small glycoprotein secreted by monocytes, endothelial cells, glycoprotein secreted by monocytes, endothelial cells, fibroblasts, synovial cells, and some tumor cells such as melanoma cells. It is structurally related to IL-8 and can activate neutrophils, whereas it induces chemotaxis, exocytosis, and a respiratory burst in neutrophils. To date, its functions on T lymphocytes have not been well established. We report here that recombinant human (rh)GRO-alpha is a potent chemoattractant for freshly isolated T lymphocytes, but not for anti-CD3 mAb-activated T lymphocytes. It attracts CD4+ and CD8+ T lymphocyte subsets to an equal extent. The migrating T lymphocytes toward rhGRO-alpha are predominantly CD45RO+ memory CD4+ and CD8+ subsets. The chemotactic migration of T lymphocytes toward rhGRO-alpha is stimulated via the IL-8 receptors on the cells. This process can be augmented by IFN-gamma and TNF-alpha, and inhibited by IL-4, IL-10, and IL-13. In addition, we also document that on T lymphocytes there exist IL-8 receptors that can be up-regulated by IFN-gamma, TNF-alpha, and IL-2. Our results demonstrate that rhGRO-alpha gene encodes for an inflammatory mediator that stimulates the directional migration of T lymphocytes. It may thus be another important mediator in the diseases in which T lymphocytes form the major constituent of the cellular infiltration.