Lung tissue mechanics and extracellular matrix composition in a murine model of silicosis.

The dynamic mechanical properties of lung tissue and its contents of collagen and elastic fibers were studied in strips prepared from mice instilled intratracheally with saline (C) or silica [15 (S15) and 30 days (S30) after instillation]. Resistance, elastance, and hysteresivity were studied during oscillations at different frequencies on S15 and S30. Elastance increased from C to silica groups but was similar between S15 and S30. Resistance was augmented from C to S15 and S30 and was greater in S30 than in S15 at higher frequencies. Hysteresivity was higher in S30 than in C and S15. Silica groups presented a greater amount of collagen than did C. Elastic fiber content increased progressively along time. This increment was related to the higher amount of oxytalan fibers at 15 and 30 days, whereas elaunin and fully developed elastic fibers were augmented only at 30 days. Silicosis led not only to pulmonary fibrosis but also to fibroelastosis, thus assigning a major role to the elastic system in the silicotic lung.     

Disseminated nocardiosis in three macaque monkeys

Extrapulmonary nocardiosis was diagnosed at necropsy in two rhesus monkeys (Macaca mulatta) and one pigtailed monkey (M. nemestrina) over a four-year period in a large primate center. Typical lesions were multiple pyogranulomatous foci in the liver, intestines, peritoneum, lung and brain. Partially acid-fast, branching, filamentous organisms were seen in all lesions. Nocardia sp. was isolated from two cases. We postulate that two of the monkeys were infected by the oral route because of the distribution of lesions.     

Sensitization of mice with wild-type and cold-adapted influenza virus variants: immune response to two H1N1 and H3N2 viruses

Two A strain influenza viruses, A/Hong Kong/123/77 (A/HK/123/77) (H1N1) and A/Queensland/6/72 (A/Qld/6/72) (H3N2), and the two cold-adapted reassortants which possess the surface antigens of these strains (CR35 and CR6, respectively) were tested for their ability both to induce primary cytotoxic T-cell (Tc cell) responses in mice and to sensitize mice for a second Tc cell response when challenged with a distantly related A strain virus, A/Shearwater/72 (H6N5). After intranasal inoculation, A/Qld/6/72 replicated to higher titers in the lung (1 to 2 log10 50% egg infective doses) than did A/HK/123/77 or either of the reassortants. A/Qld/6/72 induced higher Tc cell responses in the lung than did CR6, and both were more effective than either A/HK/123/77 or CR35 in this respect. When similar doses (10 or 10(3) hemagglutinin units) of each virus were injected intravenously into mice and the spleens were tested for Tc cell activity 6 days later, both A/Qld/6/72 and CR6 were ca. 100-fold better at inducing a primary Tc cell response than A/HK/123/77 or CR35. In contrast, the H1N1 and H3N2 viruses gave rather similar anti-hemagglutinin antibody titers (after intravenous injection) and delayed-type hypersensitivity reactions (after subcutaneous injection). If mice were primed with a low dose of these viruses (10(4) 50% egg infective doses intranasally), A/Qld/6/72 and CR6 were more effective than A/HK/123/77 or CR35 at sensitizing for a secondary Tc cell response when challenged with A/Shearwater/72, but if larger doses were given either intranasally (10(6) 50% egg infective doses) or intravenously (10 to 10(3) hemagglutinin units), all viruses sensitized the mice equally well, despite the fact the A/Shearwater/72 gives a poor primary Tc cell response in mice. Thus, the viral glycoprotein antigens can be important in determining the immunogenicity of the virus and, particularly, the class I antigen-restricted Tc cell response of the host.     

Structural transformations of arabinogalactan from the Siberian larch during mechanochemical processing and the biological properties of the products

It has been found by gel-penetrating chromatography and quantitative ¹³C NMR spectroscopy that mechanochemical processing of arabinogalactan isolated from the wood of the Siberian larch changes the molecular mass distribution, monosaccharide composition, and the degree of branching of its macromolecules. This is due to the partial destruction of polysaccharide macromolecules and subsequent recombination of resulting fragments. The intensity of these processes depends on the conditions of mechanochemical processing. Based on the data of IR and ¹³C NMR spectra, the conclusion has been drawn that no functionalization of arabinogalactan macromolecules occurs under these conditions. The toxicopharmacological properties of mechanically processed arabinogalactan have been studied. Its acute toxicity is >5000 mg/kg.     

Maleylated-BSA suppresses IFN-gamma-mediated Ia expression in murine peritoneal macrophages

Maleylated bovine serum albumin (maleyl-BSA) and other polyanionic polymers that are recognized by cell surface receptors on macrophages have been shown to induce chemotaxis, protease secretion, and tumoricidal function in this cell type. In this paper the effect of maleyl-BSA on Ia antigen expression has been evaluated. In a fashion similar to LPS, maleyl-BSA suppressed IFN-gamma-induced expression of Ia in a time- and dose-dependent manner. Also like LPS, maleyl-BSA stimulated the production and secretion of substantial amounts of PGE2 over a 24-hr period. This did not, however, appear to be the primary mechanism by which expression of Ia was suppressed, because co-treatment of the cells with indomethacin, which totally inhibited the production of PGE2, only minimally affected the suppressive activity. Surprisingly, the suppressive activity of both maleyl-BSA and LPS could be largely abrogated by co-treatment of the cells with cyclohexamide during the time period when Ia expression was sensitive to suppression. This effect was selective in that PGE2- or dibutyryl cyclic AMP-induced suppression of Ia expression was not affected by cyclohexamide treatment. The data support the concept that there are multiple molecular mechanisms involved in the negative regulation of IFN-gamma-induced Ia expression in macrophages. Such mechanisms may include, in addition to the synthesis of PGE2 and consequent elevation in intracellular levels of cyclic AMP, one or more proteins made early after treatment with either maleyl-BSA or LPS. Thus the function of some of these early gene products may be to regulate expression of functional genes such as that encoding Ia antigen.     

Interrelation of the changes in the blood rheological properties and the microcirculatory disorders in the early and late stages of experimental hyperlipoproteinemia

Experiments were made on rabbit fed an atherogenic diet (0.5 g/kg cholesterol) singly for 15 and 24 h and repeatedly for 3, 9 and 30 days. At early stages of lipid metabolism distress the interrelationship was established between blood rheological disorders and microcirculatory abnormalities. The dependence of the initial reaction of some rheological characteristics on their initial level was marked.     

Osteoarthritis of the hip: an occupational disease in farmers.

OBJECTIVE--To test the hypothesis that farmers are at high risk of hip osteoarthritis and to investigate possible causes for such a hazard. DESIGN--Cross sectional survey. SETTING--Five rural general practices. SUBJECTS--167 male farmers aged 60-76 and 83 controls from mainly sedentary jobs. All those without previous hip replacement underwent radiography of the hip. MAIN OUTCOME MEASURES--Hip replacement for osteoarthritis or radiological evidence of hip osteoarthritis. RESULTS--Prevalence of hip osteoarthritis was higher in farmers than controls and especially in those who had farmed for over 10 years (odds ratio 9.3, 95% confidence interval 1.9 to 44.5). The excess could not be attributed to any one type of farming, and heavy lifting seems the likely explanation. CONCLUSIONS--Manual handling in agriculture should be limited where possible. Consideration should be given to making hip osteoarthritis a prescribed industrial disease in farmers. There may be wider implications for the prevention of hip osteoarthritis in the general population.     

Isolation of zymogen granules from rat pancreas and characterization of their membrane proteins

A zymogen granule fraction has been isolated from rat pancreas, and its purity has been assessed by biochemical and morphological criteria. Specific activities of two marker enzymes, amylase and chymotrypsin, are increased by 4.6 and 5.4-fold, respectively, as compared to the homogenate. The purified fraction is devoid of detectable RNA, DNA and 5'-nucleotidase, glucose-6-phosphatase, and cytochrome c oxidase activities. Electron micrographs confirm the absence of mitochondria, lysosomes, and rough endoplasmic reticulum fragments. Zymogen granule membranes were isolated from this fraction on a sucrose gradient following lysis in alkaline buffer. Secretory contaminants were efficiently removed from the membranes as indicated by experiments in which labeled secretory proteins were added during the isolation procedure and secondly by measuring residual levels of amylase and chymotrypsin. Three enzyme activities were found in the membranes: thiamine pyrophosphatase, ATP-diphosphohydrolase, and low levels of acid phosphatase. Membrane proteins were solubilized by urea-Triton X-100 and separated in double-dimension (isoelectric focusing and sodium dodecyl sulfate-polyacrylamide gel electrophoresis). Isoelectric point and molecular weight of each protein band were determined.