Chronic hypersensitivity lung disease with recurrent episodes of hypersensitivity pneumonitis due to a contaminated central humidifer

A child with a 4-year history of acute and chronic respiratory symptoms of unknown aetiology was investigated for hypersensitivity pneumonitis. Lung disease due to inhalation of material from a contaminated central humidifier was suggested by the clinical history, the presence of precipitating antibodies in the serum against the humidifier water, a pulmonary response to challenge with the humidifier water, and marked improvement after removal of the humidifier. No fungi were cultured from the humidifier nor were antibodies against a number of fungal antigens identified by radioimmunoassay inhibition techniques. Antigenic material was found in the humidifier water and the household water prior to its reaching the humidifier. This antigenic material was not found in laboratory tap water supplied from the same general source (Lake Michigan) but from a different pumping station. Three of the child's siblings gave histories suggestive of a single concurrent episode of acute hypersensitivity pneumonitis and one sibling had a history suggestive of chronic hypersensitivity lung disease. No association could be found between HLA-haplotypy and disease in the patient and the siblings.     

Relationship of senescence of corn (Zea mays L.) stalk pith, cob parenchyma and first developed leaf tissues to RNA content and synthesis

In stalk parenchyma tissue of WF9 X 38-11 single corn (Zea mays L.), there was a per cell increase in RNA synthesis and a slight increase in total RNA as cells became older. In cob parenchyma tissue of WF9 X 38-11 single cross corn, both total RNA content and RNA synthesis per cell decreased with the age of cells. In first developed leaf tissue of FR43 X FR14A single cross corn, RNA synthesis increased steadily but only slightly over its life span. The pattern of RNA synthesis and destruction in senescing leaf tissue of seedlings and two sources of parenchyma tissue of maturing plants appeared to differ.     

IN VITRO ANTIOXIDANT AND ANTICANCER ACTIVITIES OF EXTRACTS FROM A FERMENTED FOOD

Solvent extracts were prepared from Manda Enzyme®, one of the fermented health foods, and their activities of radical scavenging and cancer cell growth inhibition were evaluated. Manda Enzyme® was extracted with 55% ethanol, and then fractionated into n‐hexane, chloroform, ethyl acetate, methanol‐soluble and methanol‐insoluble fractions. The antioxidant activities were in the order chloroform > ethyl acetate > other fractions and of each fraction were positively related to the amount of total phenolics and the intensity of brown color. The cancer cell growth inhibitory activities were in the order n‐hexane > chloroform > other fractions. Proliferation of HRT‐18, HCT‐48 and HepG2 human cancer cells was inhibited by the treatment of the n‐hexane fraction of Manda Enzyme® at a concentration of 400 μg/mL to the extent of 75, 89 and 90%, respectively. From these results, it is considered that Manda Enzyme® has chemically different ingredients showing strong antioxidant and anticancer activity in vitro.     

Decoupled Roles for the Atypical,Bifurcated Binding Pocket of the ybfF Hydrolase

Serine hydrolases have diverse intracellular substrates, biological functions, and structural plasticity, and are thus important for biocatalyst design. Amongst serine hydrolases, the recently described ybfF enzyme family are promising novel biocatalysts with an unusual bifurcated substrate‐binding cleft and the ability to recognize commercially relevant substrates. We characterized in detail the substrate selectivity of a novel ybfF enzyme from Vibrio cholerae (Vc‐ybfF) by using a 21‐member library of fluorogenic ester substrates. We assigned the roles of the two substrate‐binding clefts in controlling the substrate selectivity and folded stability of Vc‐ybfF by comprehensive substitution analysis. The overall substrate preference of Vc‐ybfF was for short polar chains, but it retained significant activity with a range of cyclic and extended esters. This broad substrate specificity combined with the substitutional analysis demonstrates that the larger binding cleft controls the substrate specificity of Vc‐ybfF. Key selectivity residues (Tyr116, Arg120, Tyr209) are also located at the larger binding pocket and control the substrate specificity profile. In the structure of ybfF the narrower binding cleft contains water molecules prepositioned for hydrolysis, but based on substitution this cleft showed only minimal contribution to catalysis. Instead, the residues surrounding the narrow binding cleft and at the entrance to the binding pocket contributed significantly to the folded stability of Vc‐ybfF. The relative contributions of each cleft of the binding pocket to the catalytic activity and folded stability of Vc‐ybfF provide a valuable map for designing future biocatalysts based on the ybfF scaffold.     

Docosahexaenoic Acid and Eicosapentaenoic Acid Did not Alter <Emphasis Type="Italic">trans</Emphasis>-10,<Emphasis Type="Italic">cis</Emphasis>-12 Conjugated Linoleic Acid Incorporation into Mice Brain and Eye Lipids

trans 10,cis 12‐CLA has been reported to alter fatty acid composition in several non‐neurological tissues, but its effects are less known in neurological tissues. Therefore, the purpose of this study was to determine if CLA supplementation would alter brain and eye fatty acid composition and if those changes could be prevented by concomitant supplementation with docosahexaenoic acid (DHA; 22:6n3) or eicosapentaenoic acid (EPA; 20:5n3). Eight‐week‐old, pathogen‐free C57BL/6N female mice (n = 6/group) were fed either the control diet or diets containing 0.5% (w/w) t10,c12‐CLA in the presence or absence of either 1.5% DHA or 1.5% EPA for 8 weeks. CLA concentration was significantly (P < 0.05) greater in the eye but not in the brain lipids of the CLA group when compared with the control group. The sums of saturated, monounsaturated, polyunsaturated fatty acids, and n3:n6 ratio did not differ between these two groups for both tissues. The n3:n6 ratio and concentrations of 20:5n3 and 22:5n3 were significantly greater, and those of 20:4n6, 22:4n6, and 22:5n6 were lesser in the CLA + DHA and CLA + EPA groups than in the control and CLA groups for either tissue. DHA concentration was higher in the CLA + DHA group only but not in the CLA + EPA group when compared with the CLA group for both tissues. The dietary fatty acids generally induced similar changes in brain and eye fatty acid concentration and at the concentrations used both DHA and EPA fed individually with CLA were more potent than CLA alone in altering the tissue fatty acid concentration.     

Regional difference in insulin inhibition of non-esterified fatty acid release from human adipocytes: relation to insulin receptor phosphorylation and intracellular signalling through the insulin receptor substrate-1 pathway

Increased mobilization of non-esterified fatty acids (NEFA) from visceral as opposed to peripheral fat depots can lead to metabolic disturbances because of the direct portal link between visceral fat and the liver. Compared with peripheral fat, visceral fat shows a decreased response to insulin. The mechanisms behind these site variations were investigated by comparing insulin action on NEFA metabolism with insulin receptor signal transduction through the insulin receptor substrate-1 (IRS-1) pathway in omental (visceral) and subcutaneous human fat obtained during elective surgery. Insulin inhibited lipolysis and stimulated NEFA re-esterification. This was counteracted by wortmannin, an inhibitor of phosphaditylinositol (PI) 3-kinase. The effects of insulin on antilipolysis and NEFA re-esterification were greatly reduced in omental fat cells. Insulin receptor binding capacity, mRNA and protein expression did not differ between the cell types. Insulin was four times more effective in stimulating tyrosine phosphorylation of the insulin receptor in subcutaneous fat cells (p < 0.001). Similarly, insulin was two to three times more effective in stimulating tyrosine phosphorylation of IRS-1 in subcutaneous fat cells (p < 0.01). This finding could be explained by finding that IRS-1 protein expression was reduced by 50 +/- 8% in omental fat cells (p < 0.01). In omental fat cells, maximum insulin-stimulated association of the p85 kDa subunit of PI 3-kinase to phosphotyrosine proteins and phosphotyrosine associated PI 3-kinase activity were both reduced by 50% (p < 0.05 or better). Thus, the ability of insulin to induce antilipolysis and stimulate NEFA re-esterification is reduced in visceral adipocytes. This reduction can be explained by reduced insulin receptor autophosphorylation and signal transduction through an IRS-1 associated PI 3-kinase pathway in visceral adipocytes.