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PubMed2004

Role of viruses in exacerbations of chronic obstructive pulmonary disease.

Exacerbations of chronic obstructive pulmonary disease (COPD) are a major cause of morbidity and mortality and hospital admission. Respiratory viral infections, especially rhinoviruses, are a major cause of COPD exacerbations, with upper respiratory tract infections being associated with over 50% of COPD exacerbations. The presence of an upper respiratory tract infection leads to a more severe exacerbation and a longer symptom recovery time at exacerbation. Respiratory viral infections occurring during COPD exacerbations are more likely to lead to hospitalization. Sputum inflammatory markers were found to be higher in those patients with symptoms of a common cold or where rhinovirus was detected at exacerbation, thus suggesting that viral infections lead to greater airway inflammation and thus more severe exacerbations. COPD exacerbations are associated also with systemic inflammatory effects with increases in markers such as plasma fibrinogen and interleukin-6. Respiratory viruses have also been detected when the patients are stable, and this suggests that chronic viral infection may occur. Strategies to prevent viral infection will have a significant effect on the morbidity of COPD and will improve quality of life.

Common Cold↗
PubMed1992

Intracellular catabolism of radiolabeled anti-mu antibodies by malignant B-cells.

The endocytosis and degradation of 125I-labeled anti-mu monoclonal antibody DA4-4 by a Burkitt's lymphoma cell line was investigated using biochemical, chromatographic, electrophoretic, radioautographic, and electron microscopic techniques. 125I-DA4-4 was rapidly internalized by Ramos cells and routed from endosomes to lysosomes. Proteolysis of radiolabeled antibodies began in a late endosomal compartment, but lysosomes were primarily responsible for the terminal degradation of 125I-DA4-4. Catabolism of 125I-DA4-4 could be inhibited by 74-95% by blocking its delivery to late endosomes and lysosomes by incubation at 18 degrees C, by neutralizing the pH in intracellular organelles with monensin or ammonium chloride, or by inhibiting lysosomal enzymes with leupeptin. Radiolabeled antibodies synthesized using the chloramine T or Iodo-Gen techniques were degraded three times faster than conjugates made using a nonmetabolizable 125I-tyramine cellobiose adduct. Five major intermediate metabolites (Mr 48,000, 42,000, 25,000, 15,000, and 10,000) were generated during the intracellular catabolism of 125I-DA4-4, but 125I-tyrosine was responsible for 95% of the small-molecular-weight metabolites released by cells into the culture medium. We anticipate that a full comprehension of the catabolism of radiolabeled antibodies by tumor cells will make possible the development of clinical interventions which will enhance the retention of radioimmunoconjugates by hematologic malignancies and improve the efficacy of radioimmunotherapy.

Animals↗
PubMed1986

Autoimmune hemolytic anemia due to monoclonal IgM lambda anti-Tja (Anti-P+1+Pk).

A patient with autoimmune hemolytic anemia of the cold antibody type is described. The monoclonal autoantibody had mu heavy and lambda light chains and Tja blood group specificity. The antibody resulted in acute hemolysis responsive to steroid treatment and appeared simultaneously with an increase in CMV titer.

Journal Article↗
PubMed1998

Cold rescue of the thermolabile tailspike intermediate at the junction between productive folding and off-pathway aggregation.

Off-pathway intermolecular interactions between partially folded polypeptide chains often compete with correct intramolecular interactions, resulting in self-association of folding intermediates into the inclusion body state. Intermediates for both productive folding and off-pathway aggregation of the parallel beta-coil tailspike trimer of phage P22 have been identified in vivo and in vitro using native gel electrophoresis in the cold. Aggregation of folding intermediates was suppressed when refolding was initiated and allowed to proceed for a short period at 0 degrees C prior to warming to 20 degrees C. Yields of refolded tailspike trimers exceeding 80% were obtained using this temperature-shift procedure, first described by Xie and Wetlaufer (1996, Protein Sci 5:517-523). We interpret this as due to stabilization of the thermolabile monomeric intermediate at the junction between productive folding and off-pathway aggregation. Partially folded monomers, a newly identified dimer, and the protrimer folding intermediates were populated in the cold. These species were electrophoretically distinguished from the multimeric intermediates populated on the aggregation pathway. The productive protrimer intermediate is disulfide bonded (Robinson AS, King J, 1997, Nat Struct Biol 4:450-455), while the multimeric aggregation intermediates are not disulfide bonded. The partially folded dimer appears to be a precursor to the disulfide-bonded protrimer. The results support a model in which the junctional partially folded monomeric intermediate acquires resistance to aggregation in the cold by folding further to a conformation that is activated for correct recognition and subunit assembly.

Bacteriophage P22↗
PubMed2005

Thermally induced changes in lipid composition of raft and non-raft regions of hepatocyte plasma membranes of rainbow trout.

In poikilotherms, increases in plasma membrane (PM) cholesterol and an increase in the degree of lipid acyl chain saturation commonly accompany an increase in growth temperature. This has typically been interpreted in terms of membrane fluidity/order homeostasis, but these changes would also be expected to stabilize the structure of PM rafts against thermal perturbation. Rafts are microdomains that organize the molecules of many signaling cascades and are formed as a result of interactions between lipids with saturated acyl chains and cholesterol. No study to date has examined the thermally induced compositional changes of raft and non-raft regions of the PM separately. In this study we have measured the phospholipid class composition and fatty acid composition of raft-enriched (raft) and raft-depleted PM (RDPM) of hepatocytes from trout Oncorhynchus mykiss acclimated to 5 degrees C and 20 degrees C. In the raft, warm acclimation was associated with a reduction in the proportion of phosphatidylcholine from 56% to 30% while phosphatidylserine and phosphatidylinositol each increased from 8% to approximately 20% of the total phospholipid. Additionally, there were significantly fewer unsaturated fatty acids in the raft lipids from warm-acclimated (61%) than from the cold-acclimated trout (68%). In contrast, there were no significant changes in phospholipid class or acyl chain unsaturation in the RDPM. These data suggest that changes in raft lipid composition, rather than the PM as a whole, are particularly important during thermal acclimation.

Acclimatization↗
PubMed2002

A mitochondrial complex I defect impairs cold-regulated nuclear gene expression.

To study low-temperature signaling in plants, we previously screened for cold stress response mutants using bioluminescent Arabidopsis plants that express the firefly luciferase reporter gene driven by the stress-responsive RD29A promoter. Here, we report on the characterization and cloning of one mutant, frostbite1 (fro1), which shows reduced luminescence induction by cold. fro1 plants display reduced cold induction of stress-responsive genes such as RD29A, KIN1, COR15A, and COR47. fro1 leaves have a reduced capacity for cold acclimation, appear water-soaked, leak electrolytes, and accumulate reactive oxygen species constitutively. FRO1 was isolated through positional cloning and found to encode a protein with high similarity to the 18-kD Fe-S subunit of complex I (NADH dehydrogenase, EC 1.6.5.3) in the mitochondrial electron transfer chain. Confocal imaging shows that the FRO1:green fluorescent protein fusion protein is localized in mitochondria. These results suggest that cold induction of nuclear gene expression is modulated by mitochondrial function.

Acclimatization↗
PubMed2003

Synergistic effects of dietary iron and omega-3 fatty acid levels on survival of farmed Atlantic salmon, Salmo salar L., during natural outbreaks of furunculosis and cold water vibriosis.

The present study demonstrates that farmed Atlantic salmon, Salmo salar, health is positively and significantly affected by synergistic effects between very long-chain polyunsaturated fatty acids of the n-3 family eicosapentaenoic acid/docosahexaenoic acid (EPA/DHA) and iron, where positive effects of high dietary levels of EPA/DHA are enhanced when combined with low levels of iron. Based on cumulative mortalities in the different experimental groups, relative percentage of survival (RPS) for the high EPA/DHA-low iron group was 70% during an outbreak of furunculosis and 96% during an outbreak of cold water vibriosis compared with the controls. A non-additive effect between EPA/DHA and iron was confirmed by statistical analyses that revealed a significant effect of EPA/DHA alone and an interaction of iron with EPA/DHA. Liver cell cultures treated with EPA/DHA revealed that the synergistic effect could be related to an EPA/DHA dependent regulation of mRNA for proteins important for transport (transferrin) and storage (ferritin) of iron in the salmon. In keeping with this finding, the transcriptional down-regulation of iron metabolism in vitro was reflected in decreased in vivo iron stores with increasing levels of dietary EPA/DHA. Hence, to avoid overloading of the iron transport/storage-systems resulting in increased susceptibility to bacterial infections, high levels of dietary EPA/DHA should be accompanied by low levels of dietary iron.

Animals↗
PubMed1993

The stability of serum hepatitis C viral RNA in various handling and storage conditions.

To investigate whether certain handling and storage conditions of serum samples could alter the sensitivity and specificity of the hepatitis C virus (HCV) RNA assay, we studied serum samples obtained from five patients known to be positive for HCV RNA and two patients with autoimmune chronic active hepatitis. Samples were subjected to one of the following conditions: (1) immediate storage at -20 degrees C, (2) five freeze-thaw cycles, (3) storage at 4 degrees C for 5 days, and (4) storage at room temperature for 5 days. Detection of HCV RNA was performed by polymerase chain reaction. Titers of HCV RNA were determined by serial end point dilutions. We found that the titer of HCV RNA was reduced by only one logfold in samples subjected to conditions 2 through 4 in two of the five patients. False-positive results were not seen with the serum samples that were subjected to similar conditions from the two negative control patients. We conclude that serum HCV RNA is resistant to degradation under routine laboratory handling and storage conditions.

Blood Preservation↗
PubMed1988

Amino acid and glucose uptake by rat brown adipose tissue. Effect of cold-exposure and acclimation.

The net uptake/release of glucose, lactate and amino acids from the bloodstream by the interscapular brown adipose tissue of control, cold-exposed and cold-acclimated rats was estimated by measurement of arteriovenous differences in their concentrations. In the control animals amino acids contributed little to the overall energetic needs of the tissue; glucose uptake was more than compensated by lactate efflux. Cold-exposure resulted in an enhancement of amino acid utilization and of glucose uptake, with high lactate efflux. There was a net glycine and proline efflux that partly compensated the positive nitrogen balance of the tissue; amino acids accounted for about one-third of the energy supplied by glucose to the tissue. Cold-acclimation resulted in a very high increase in glucose uptake, with a parallel decrease in lactate efflux and amino acid consumption. Branched-chain amino acids, however, were more actively utilized. This was related with a much higher alanine efflux, in addition to that of glycine and proline. It is suggested that most of the glucose used during cold-exposure is returned to the bloodstream as lactate under conditions of active lipid utilization, amino acids contributing their skeletons largely in anaplerotic pathways. On the other hand, cold-acclimation resulted in an important enhancement of glucose utilization, with lowered amino acid oxidation. Amino acids are thus used as metabolic substrates by the brown adipose tissue of rats under conditions of relatively scarce substrate availability, but mainly as anaplerotic substrates, in parallel to glucose. Cold-acclimation results in a shift of the main substrates used in thermogenesis from lipid to glucose, with a much lower need for amino acids.

Adipose Tissue, Brown↗
PubMed1984

A new interstellar molecule: tricarbon monoxide.

The cold dark interstellar Taurus Molecular Cloud One (TMC-1) is a rich source of acetylenic and polyacetylenic molecular species. As well as linear closed-shell molecules (H(C triple bond C)nCN) and symmetric rotors (CH3C triple bond CH, CH3C triple bond CCN), several radicals (C triple bond CH, C triple bond CCN, (C triple bond C2H) have also been identified, many of which had not been studied previously in the laboratory. Whether the observed abundances can be understood in terms of purely gas-phase ion-molecule chemical schemes, which produce reasonable agreement for the simplest polyatomic species, is unclear; alternative models involving the particulate interstellar grains as catalysts or sources have also been suggested. We now report the detection in TMC-1 of a new molecule, tricarbon monoxide (C3O), whose pure rotational spectrum has only very recently been studied in the laboratory. As C3O is the first known interstellar carbon chain molecule to contain oxygen, its existence places an important new constraint on chemical schemes for cold interstellar clouds. In fact, the observed abundance of tricarbon monoxide fits quite well into our model of galactochemistry.

Astronomical Phenomena↗
PubMed1983

Pseudothrombocytopenia with cold-type platelet agglutinins.

Pseudothrombocytopenia is an in vitro phenomenon of platelet agglutination and clumping in the presence of EDTA on the electronical measurement of platelet count. Agglutinins reacting with platelet antigens belong to one heavy and one light chain of immunoglobulins with or without complement by immunofluorescence. The platelets are markedly agglutinated in EDTA, but scarcely in the presence of other anticoagulants. Agglutinations seem to occur more readily at cold temperature rather than at 37 degrees C.

Agglutinins↗
PubMed2002

Evidence for involvement of a hydrophobic patch in framework region 1 of human V4-34-encoded Igs in recognition of the red blood cell I antigen.

The monoclonal IgM cold agglutinins that bind to the I/i carbohydrate Ags on the surface of RBCs all have Ig H chains encoded by the V4-34 gene segment. This mandatory use indicates that distinctive amino acid sequences may be involved in recognition. Critical amino acids exist in framework region 1 (FR1) of V4-34-encoded Ig, and these generate a specific Id determinant which apparently lies close to the I binding site. However, I binding by Id-expressing Ig can be modulated by sequences in complementarity-determining region (CDR)(H)3. Examination of the crystal structure of an anti-I cold agglutinin has revealed a hydrophobic patch in FR1 involving residue W7 on beta-strand A and the AVY motif (residues 23-25) on beta-strand B. In this study we used mutagenesis to show that each of the strand components of the hydrophobic patch is required for binding the I carbohydrate Ag. In addition, the crystal structure reveals that amino acids in the carboxyl-terminal region of CDR(H)3 form a surface region adjacent to the hydrophobic patch. We propose that the I carbohydrate Ag interacts simultaneously with the entire hydrophobic patch in FR1 and with the outside surface of CDR(H)3. This interaction could leave most of the conventional binding site available for binding other Ags.

Agglutinins↗
PubMed2000

Expression and distribution of heme oxygenase-1 and -2 in rat brown adipose tissue: the modulatory role of the noradrenergic system.

To investigate whether brown adipose tissue (BAT) expresses the inducible (HO-1) and the constitutive (HO-2) isoform of heme oxygenase, reverse transcriptase-polymerase chain reaction, Western blotting and immunohistochemistry were performed on interscapular BAT (IBAT) from rats acclimated at environmental temperature or exposed to cold. Both HO isoforms were detected in rat IBAT. They were immunolocalized in the cytoplasm and/or nuclei of brown adipocytes, in parenchymal capillaries, arteries and in some veins and nerves. Whereas cold exposure did not affect HO-2 expression, it significantly increased the expression of HO-1, both at mRNA (about 3-fold) and protein (about 2-fold) levels, reflecting the increased expression of HO-1 in the brown adipocytes and endothelial cells of parenchymal capillaries. Western blotting of cytosolic and nuclear protein extracts from cultured differentiated brown adipocytes showed that HO-1 and HO-2 are indeed localized in the cytosol and nuclei of brown adipocytes, and that noradrenaline stimulation significantly increased their amount in cytosol but not in the nuclear fraction.

Acclimatization↗
PubMed1996

Exposure-response relationship for vibration-induced white finger among forestry workers.

The relation between the occurrence of white finger and vibration exposure was investigated in a group of 222 forestry workers using chain saws. The forestry workers and 195 controls never exposed to hand-transmitted vibration were interviewed by occupational health physicians. The diagnosis of vibration-induced white finger (VWF) was made on the basis of subjective symptoms of finger blanching and the results of a cold test with plethysmographic measurement of finger systolic blood pressure. Vibration was measured on a representative sample of AV and non-AV chain saws. Daily vibration exposure was assessed in terms of 8 h energy-equivalent frequency-weighted acceleration [A(8)]. A lifetime vibration dose was estimated for each of the forestry workers. The overall prevalence of VWF among the forestry workers was 23.4%. Raynaud's phenomenon was discovered in 2.6% of the controls. In the forestry workers, the risk of VWF showed positive increments with each increment of vibration dose, suggesting a monotonic dose-response relationship. The responsiveness to cold in the digital arteries of the forestry workers was also found to increase with increasing vibration dose. The estimated relation between VWF and vibration exposure showed that the expected occurrence of VWF increased in approximately linear proportion to either A(8) (with exposure duration unchanged) or the number of years of exposure (with equivalent acceleration unchanged). In this study of VWF among forestry workers the estimated exposure-response relation showed that if the magnitude of vibration acceleration is doubled, the total duration of exposure should be halved to produce an equivalent effect. On the basis of the assessment of vibration exposure, the estimated risk for VWF in the study population was found to be lower than that predicted by the International Standard ISO 5349. The results of this study tend to support the vibration exposure levels currently under discussion within the European Union.

Adult↗
PubMed1995

Dose-response relation for vascular disorders induced by vibration in the fingers of forestry workers.

OBJECTIVES: To study the relation between the prevalence of vascular disorders (white finger) and vibration exposure in a group of 222 forestry workers, of whom 164 (73.9%) had work experience limited to antivibration (AV) chain saws only and 58 (26.1%) had operated both non-AV and AV chain saws. METHODS: The chain saw operators and 195 control workers never exposed to hand transmitted vibration were interviewed with health and workplace assessment questionnaires. The diagnosis of vibration induced white finger (VWF) was made on the basis of subjective symptoms of finger blanching and the results of a cold test with plethysmographic measurement of systolic blood pressure of the finger. Vibration was measured on a representative sample of AV and non-AV chain saws. Daily vibration exposure was assessed as eight hour energy equivalent frequency weighted acceleration (A(8)). A lifetime vibration dose was estimated for each of the forestry workers. RESULTS: The overall prevalence of VWF among the forestry workers was 23.4%. The diagnosis of VWF was made in 13.4% of the forestry workers who handled only AV chain saws and in 51.7% of those who had also operated non-AV chain saws in the past. Raynaud's phenomenon was found in 2.6% of the controls. In the forestry workers, the risk for VWF showed positive increments with each increment of vibration dose, suggesting a monotonic dose-response relation. The responsiveness to cold in the digital arteries of the forestry workers was also found to increase with increasing vibration dose and severity of VWF. The estimated relation between VWF and vibration exposure showed that the expected prevalence of VWF increased almost linearly to either A(8) (with exposure duration unchanged) or the number of years of exposure (with equivalent acceleration unchanged). CONCLUSIONS: In this study of VWF among forestry workers, the estimated dose-response relation showed that if the magnitude of vibration acceleration is doubled, the total duration of exposure should be halved to produce an equivalent effect. On the basis of the assessment of vibration exposure, the estimated risk for VWF in the study population was found to be lower than that predicted by the international standard ISO 5349. These findings suggest a revision of the risk estimates for VWF currently provided by ISO 5349.

Case-Control Studies↗