Biomedical subjects
Publications and source records attributed to S Louie.
Circulating immune complexes occurred during pulmonary hemorrhage in a pregnant patient with idiopathic pulmonary hemosiderosis, an association not previously reported. The patient required mechanical ventilation, but recovered; after a prolonged hospitalization, she was delivered of a healthy infant without further complications.
Ozone (O3) is a powerfully oxidizing pollutant gas. Its toxic effects to animals appear to be worsened by coexposures to acid-generating compounds such as oxides of nitrogen and sulfur. Ozone (16 ppm) oxidizes ascorbic acid and uric acid (two important antioxidants in lung lining fluids) at equal rates at pH 5.0 or pH 7.4. Loss of intrinsic fluorescence and formation of carbonyls in albumin exposed to O3 are similar at both pH values. However, albumin-SH groups are lost much faster on exposure to O3 at pH 7.4 than at acidic pH values. A similar slower rate of -SH group disappearance at acidic pH is seen when cysteine or reduced glutathione are exposed to O3. We suggest that the ability of reduced glutathione, albumin, and other proteins containing -SH groups to scavenge O3 in the respiratory tract is impaired at low pH and that this effect could contribute to the aggravation of O3 toxicity.
Hypochlorous acid (HOCI) is a powerful oxidizing and chlorinating agent produced by the neutrophil enzyme myeloperoxidase. The antioxidant defenses of freshly prepared human plasma against HOCI/OCI- were explored. Addition of HOCI/OCI- to plasma caused rapid oxidation of ascorbic acid and thiol (-SH) groups but not of uric acid. Plasma -SH groups (which are known to be largely located on albumin) were quantitatively the most important scavenger of HOCI/OCI-, but adding extra ascorbate to plasma caused this molecule to have a more important scavenging role against HOCI/OCI-. Added HOCI/OCI- produced no detectable lipid peroxidation in plasma or depletion of lipid-soluble antioxidants (alpha-tocopherol or ubiquinol-10). No evidence of oxidative damage to protein amino acid residues (other than -SH) was detected by the carbonyl assay. It seems that -SH groups are a major target of attack by HOCI/OCI- in vivo, and plasma albumin may be an important protective antioxidant. Ascorbic acid might also play a protective role, especially in individuals supplemented with this vitamin. Ascorbate might also be important in extracellular fluids with low albumin concentrations such as synovial, respiratory tract lining, and cerebrospinal fluids.
To test the hypothesis that deferoxamine (DFO) may protect the lung against the acute toxicity of ozone (O3), male Sprague-Dawley rats (250 to 300 gm) were tracheally insufflated before exposure to O3 (2 ppm for 4 hours) with DFO (25 mg/kg), ferric-DFO, or sterile water. Measurements of bronchoalveolar lavage fluid (BALF) protein, ascorbate, hydrogen peroxide, and lipid hydroperoxides were made immediately after O3 exposure and 12 and 24 hours later. DFO (25 mg/kg) decreased BALF protein concentration (p < 0.05) and was associated with higher BALF ascorbate concentrations (p < 0.01) in O3-exposed animals. Ferric-DFO did not show these protective effects. No peroxides were found in BALF from any control or O3-exposed animals (detection limit: H2O2, 1 pmol; lipid hydroperoxides, 0.3 pmol). Higher DFO doses (50 mg/kg and 100 mg/kg) did not decrease BALF protein concentration immediately after O3 exposure or 12 hours later. Indeed, the highest dose was toxic to O3-exposed animals. Although DFO is able to protect against O3-induced lung damage in rats, apparently by chelating iron, its effect dose range appears to be narrow.
Nitrogen dioxide (NO2.) is often present in inhaled air and may be generated in vivo from nitric oxide. Exposure of human blood plasma to NO2. caused rapid losses of ascorbic acid, uric acid and protein thiol groups, as well as lipid peroxidation and depletions of alpha-tocopherol, bilirubin and ubiquinol-10. No increase in protein carbonyls was detected. Supplementation of plasma with ascorbate decreased the rates of lipid peroxidation, alpha-tocopherol depletion and loss of uric acid. Uric acid supplementation decreased rates of lipid peroxidation but not the loss of alpha-tocopherol. We conclude that ascorbic acid, protein -SH groups, uric acid and alpha-tocopherol may be important agents protecting against NO2. in vivo. If these antioxidants are depleted, peroxidation of lipids occurs and might contribute to the toxicity of NO2..
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Oxidative stress has been implicated in the adult respiratory distress syndrome (ARDS). In this study, we determined the levels of selected antioxidants in the plasma of 25 patients with ongoing ARDS and 16 healthy control subjects. We also examined these plasmas and pulmonary edema fluid of ARDS patients for lipid hydroperoxides. Both ascorbate and ubiquinol-10 concentrations in ARDS plasma were significantly lower than in normal plasma. alpha-Tocopherol concentrations, when standardized to total plasma cholesterol, were not lower in ARDS patients than in normal subjects. A pattern of antioxidant levels virtually identical to that observed in ARDS plasma was obtained after in vitro incubation of healthy plasma with stimulated polymorphonuclear leukocytes: very low ascorbate, decreased ubiquinol-10, and unchanged alpha-tocopherol concentrations. Nanomolar concentrations of lipid hydroperoxides were found in pulmonary edema fluid of ARDS patients, but not in plasma, nor in the plasma of healthy individuals, when a sensitive and selective chemiluminescence assay for hydroperoxides was used. ARDS patients also showed significant decreases in plasma levels of cholesterol esters in conjunction with discoidal high-density lipoprotein profiles, indicating a decrease in lecithin-cholesterol acyltransferase activity. We conclude that ARDS is associated with oxidative stress, possibly exerted by oxidants released from activated phagocytic leukocytes, and major changes in plasma cholesterol metabolism.
Diadenosine tetraphosphate (AP4A), a competitive inhibitor of ADP-induced platelet aggregation, was tested as an antithrombotic agent in a rabbit intracarotid thrombosis model previously shown to be sensitive to antiplatelet agents. Eighty-four percent of control rabbits formed clots. The infusion of AP4A at a dose of 50 mg/kg over 2 hours reduced the incidence of thrombosis to 56% (p less than 0.05). Blood AP4A increased 125-fold at the end of infusion, but was completely cleared within 10 minutes. Plasma ATP showed bimodal early and late increases. Platelets recovered from AP4A-treated rabbits exhibited a pattern of reduced reactivity to ADP, but not to collagen, similar to platelets exposed to AP4A in vitro. This study shows that AP4A may be a potentially useful antithrombotic agent.
All five siblings (three boys and two girls, aged 1.5-9 years) in a family developed hemolytic-uremic syndrome associated with verotoxin-producing Escherichia coli O157:H7 at a lakeside vacation cottage during the fall of 1985. All five were hospitalized and made a full recovery. Both parents remained asymptomatic, and neither had evidence of this infection. In four children who were investigated prospectively, free verotoxin was still detectable in the stools for between 3 and 7 weeks. The prodromal diarrheal illness in the children occurred over a 10-day period. The epidemic curve was consistent with a point-source outbreak, but continuous exposure or person-to-person transmission could not be ruled out. The source of the infection was not identified.
Verocytotoxin (VT)-producing Escherichia coli is closely associated with hemorrhagic colitis and hemolytic uremic syndrome. The diagnosis of this infection requires the demonstration of VT activity in fecal filtrates or the isolation of VT-producing E. coli from stools. To improve the sensitivity of the Vero cell assay for detecting VT, we investigated the interaction between this toxin and cycloheximide and puromycin, agents which, like VT and the related Shiga toxin, are protein synthesis inhibitors. Cycloheximide-treated cells were found to be about eightfold more sensitive to VT, this effect being most pronounced when the drug was added before the toxin. In contrast, puromycin treatment had an antagonistic effect in that it decreased the sensitivity of the cells to VT. In assays of VT in fecal filtrates, the addition of cycloheximide (at 4 to 8 micrograms/ml) increased the sensitivity without affecting the specificity of the assays. Likewise, the use of cycloheximide led to an increase in the sensitivity of the serum VT-neutralizing antibody test by a factor of over eightfold.
A 77-yr-old woman presented with a malignant fibrous histiocytoma (MFH) of the trachea 11 yr after right subtotal thyroidectomy and delivery of 5,400 rads to the neck for infiltrating papillary thyroid carcinoma. The tumor developed in the irradiated area. Postirradiation MFH tends to occur in subcutaneous tissues, and is rare in lung parenchyma or airways.
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Penicillamine is the drug of choice in Wilson's disease and a therapeutic alternative in rheumatoid arthritis. Autoimmune complications associated with penicillamine include cases resembling systemic lupus erythematosus and Goodpasture's syndrome. We report a case of diffuse pulmonary hemorrhage associated with prolonged penicillamine use in a patient with Wilson's disease with evidence of circulating immune complexes and complement activation, but without serologic or morphologic evidence of systemic lupus erythematosus, Goodpasture's syndrome or renal disease.
Demonstration of the fistulous tract linking pancreatic pseudocysts to the mediastinum and pleural cavity has diagnostic and therapeutic implications. In four cases, pseudocyst drainage through the esophageal and aortic diaphragmatic crus into the mediastinum and pleural cavity was delineated by computed tomography. In two cases, significant pericardial effusions were demonstrated. Computed tomography offers an effective diagnostic method when treatment is dependent on anatomic localization of the disrupted pseudocyst and its intrathoracic drainage tract.
A 26-year-old asthmatic female developed severe asthma within a few hours of receiving three oral doses of 0.4 mg ergometrine maleate for the control of postpartum haemorrhaging. This experience and two previous reports of bronchospasm in asthmatic subjects following ergometrine suggested that ergometrine altered airway smooth muscle tone. In the present investigation the effect of ergometrine was studied on canine tracheal smooth muscle strips. Ergometrine (10(-9) M-10(-4) M) induced contraction of canine tracheal smooth muscle. The concentration causing 50% of maximal contraction (EC50) was 4.73 X 10(-8) M. The acetylcholine EC50 was not altered by ergometrine (10(-9) M or 10(-8) M); however, acetylcholine (10(-4) M and 10(-3) M) induced contractions were enhanced by ergometrine (10(-8) M). The data suggest that ergometrine maleate may cause broncho-constriction in some patients with asthma.