Biomedical subjects
Publications and source records attributed to J M Fine.
Airway inflammation due to exposure to a wide variety of agents encountered in the workplace is a major cause of occupational asthma. This article reviews major examples of occupational asthma linked to airway inflammation, including their epidemiology, pathophysiology, and clinical course.
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We studied the relationship between duration and concentration of exposure in SO2-induced bronchoconstriction in 8 asthmatic subjects. On separate days, we administered SO2 in humidified air through a mouthpiece at 2 concentrations (0.5 and 1.0 ppm) for 3 time periods (1, 3, and 5 min) during eucapnic hyperpnea (60 L/min). Humidified air was administered for 5 min as a control. Bronchoconstriction was assessed by measurement of specific airway resistance (SRaw). The magnitude of the bronchoconstrictor response to both concentrations of SO2 increased progressively over the 3 time periods studied. The mean (+/- SE) increase in SRaw (in L x cm H2O/L/s) and percent increase above baseline (in parentheses) after each exposure to SO2 were as follows: 2.5 +/- 0.3 (34%) after 0.5 ppm for 1 min; 7.5 +/- 4.7 (93%) after 1.0 ppm for 1 min; 13 +/- 3.2 (173%) after 0.5 ppm for 3 min; 31.4 +/- 7.4 (395%) after 1.0 ppm for 3 min; 19.6 +/- 4.0 (234%) after 0.5 ppm for 5 min; 44.1 +/- 9.8 (580%) after 1.0 ppm for 5 min; 3.5 +/- 1.5 (46%) after humidified air for 5 min. For the group, the increases in SRaw caused by inhalation of both concentrations of SO2 for 1 min were small. However, 2 of 8 subjects did develop large increases in SRaw and chest tightness after inhalation of 1.0 ppm for 1 min. Seven of 8 subjects developed wheezing, chest tightness, or dyspnea and used an inhaled bronchodilator after inhalation of 0.5 ppm for 3 and 5 min and 1.0 ppm for 3 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)
Sulfur dioxide (SO2) and sulfites are well-described causes of bronchoconstriction in persons with asthma that are chemically related and, therefore, may share a common mechanism of action. When either sulfur species dissolves in aqueous solutions, a pH-dependent equilibrium is established predominantly among bisulfite ion (HSO3-), sulfite ion (SO3=), and SO2. In addition, hydrogen ions may be released. To assess the relative bronchoconstricting potencies of these chemical forms and the role of acidity caused by the release of hydrogen ions in SO2- and sulfite-induced bronchoconstriction, we administered to 10 asthmatic subjects nebulized sodium sulfite (Na2SO3) solutions at pH 9 containing 95% sulfite, at pH 6.6 containing 80% bisulfite, and at pH 4 containing 99% bisulfite but greater than an order of magnitude more SO2 than the pH 6.6 solutions. Subjects inhaled increasing concentrations of aerosolized Na2SO3 at each pH during 1 min of tidal breathing. Subjects also breathed buffered acetic acid aerosols with the same acidity of the pH 4 Na2SO3 solutions to control for the airway effects of acid aerosols. To assess sensitivity to SO2 gas, subjects inhaled increasing concentrations of SO2 during eucapneic hyperpnea. Bronchoconstrictor response was assessed by measuring specific airway resistance (SRaw) before and after each challenge. Nine of the 10 subjects developed bronchoconstriction after inhaling the Na2SO3 aerosols at all 3 levels of pH and the SO2 gas. The mean concentration of Na2SO3 solution calculated to increase SRaw by 100% above baseline was significantly different (p less than 0.01) at the various levels of pH: pH 4 (0.17 mg/ml) less than pH 6.6 (0.49 mg/ml) less than pH 9 (2.10 mg/ml).(ABSTRACT TRUNCATED AT 250 WORDS)
We evaluated the importance of pH, titratable acidity, and specific chemical composition in acid aerosol-induced bronchoconstriction in 8 asthmatic subjects. We administered aerosols of HCl and H2SO4 at pH 2.0 in an unbuffered state and buffered with glycine. The buffered acids were given in order of increasing titratable acidity (defined as the number of ml of 1 N NaOH required to neutralize 100 ml of acid solution to pH 7.0). Each set of buffered or unbuffered acid aerosols was given on a separate day and each aerosol was inhaled through a mouthpiece during 3 min of tidal breathing. Bronchoconstriction was assessed by measurement of specific airway resistance (SRaw) before and after inhalation of each aerosol. SRaw increased by more than 50% above baseline in 1 of 8 subjects after inhalation of unbuffered HCl and in no subjects after inhalation of unbuffered H2SO4, even at pH 2.0. In contrast, SRaw increased by greater than 50% in all 8 subjects after inhalation of HCl and glycine at pH 2.0 and 7 of 8 subjects after inhalation of H2SO4 and glycine at pH 2.0. The mean titratable acidity required to increase SRaw by 50% above baseline was calculated for each challenge by linear interpolation; these values for H2SO4 and glycine (5.1 ml of 1 N NaOH) and HCl and glycine (2.2 ml of 1 N NaOH) were slightly, but significantly, different (p = 0.01) and were considerably higher than the titratable acidity of the unbuffered acids at pH 2 (1.0 ml of 1 N NaOH).(ABSTRACT TRUNCATED AT 250 WORDS)
The airway edema that develops in guinea pigs after exposure to toluene diisocyanate (TDI) requires the presence of polymorphonuclear leukocytes (PMN). To determine whether this airway edema is mediated by the release of hydrogen peroxide from PMN, we treated animals intravenously with catalase bound to polyethylene glycol and examined the extravasation of Evans blue dye into the tracheal wall after exposure to air or 3 ppm TDI for 1 h. Catalase (25,000, 100,000, and 300,000 IU/kg) caused a dose-dependent inhibition of the TDI-induced increase in dye extravasation. However, treatment with catalase, inactivated at the peroxide binding site with 3-aminotriazole, inhibited dye extravasation after exposure to TDI as effectively as the equimolar 100,000 IU/kg dose of active catalase. Injection of polyethylene glycol alone was without effect. Dose-dependent decreases in extravascular migration of PMN and in circulating PMN also were noted after catalase treatment. These results suggest that the catalase preparations used in these studies inhibited the PMN-dependent airway edema by an effect other than hydrogen peroxide scavenging. Examination of this and other commercially available catalase preparations revealed trace concentrations of endotoxin at levels that could be responsible for the observed effects on PMN function. Treatment of animals with doses of Escherichia coli endotoxin similar to those inadvertantly administered to the catalase-treated groups (0.1 ng/kg to 100 ng/kg, intravenously) inhibited TDI-induced extravasation of Evans blue dye in a dose-dependent manner. These results suggest that contaminating endotoxin may contribute to some of the protective effects of preparations of catalase observed in previous studies of vascular permeability.
The relative mobility of albumin and proalbumin genetic variants was estimated by means of cellulose acetate electrophoresis performed with three buffer systems at different pH (8.6, 5.0, and 6.9) after addition of a reference protein and dilution of sera. Numerous experiments using samples of reference variants corroborated the accuracy and reproducibility of this technique. The estimation of the variants' relative mobility at three pH allowed us to distinguish three fast-moving variants (Gent, Vanves, and Reading) and five slow-moving variants (Sondrio, Roma, Christchurch, Lille, and B) in the French population. The frequency of alloalbuminemia in this population is .0004 and is characterized by the high occurrence of albumin B and of the two proalbumin variants, Christchurch and Lille. In order to classify the variants of European origin, the methodology that we developed, owing to its more resolutive possibilities, should be employed as a first step in their identification until establishment of a structural nomenclature making mention of the amino acid substitution characterizing each variant.
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This paper reports a unique familial occurrence of Waldenström's macroglobulinemia (WM) in monozygotic twins. The determination of twin monozygosity has been performed by electrophoretic and immunological typing of genetic systems (erythrocyte blood groups, leucocyte antigens and serum protein polymorphism). The two monoclonal IgM differ one from the other by their light chain type and their idiotypic determinants. Although a genetic predisposition to WM exists in these twins, the gene recombination leading to idiotypic specificity and light chain assortment occurs independently of the monoclonal malignant involvement.
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Circulating proalbumin in humans has been described in two distinct events: genetic variants of proalbumin related to mutations at the cleavage site, and normal proalbumin related to an abnormal cleaving enzyme system. We report a case of acquired proalbuminemia that appeared after an acute episode of hepatitis related to the delta agent, in a chronic carrier of hepatitis B virus. This component, not present in normal plasma, was identified as proalbumin by immunological methods. It was indistinguishable from the molecule normally present in hepatocytes as judged by electrophoretic mobility, limited susceptibility to tryptic digestion, and its inability to bind labeled Ni. We suggest that this release of proalbumin is related to the concurrent presence of both hepatitis B and delta virus in some of the infected hepatocytes.
Monoclonal gammopathies (M.G.) are a group of disorders characterized by the proliferation of a single clone of plasma-cells that produce a Monoclonal Immunoglobulin (M-Ig). The presence of M-Ig can be demonstrated by electrophoresis in the patient' serum and identified by immunoelectrophoresis as a molecule containing two heavy chains of a single class and two light chains of a single type. In M.G. of malignant origin, free light chains (Bence Jones Proteins) can be evidenced in the concentrated urines. The fact that M.G. may be more frequent in certain families show the existence of a familial predisposition of this disease whereas its origin is still unknown. M.G. are often associated with malignant proliferation of B lymphocytes such as multiple myeloma, Waldenström's macroglobulinemia, heavy chain disease as well as some other lymphoproliferative disorders. However, in a certain number of cases, the malignant origin of the M.G. was not proved, because M-Ig can occur in the serum of people apparently in good health and without clinical or hematological features (asymptomatic "benign" M.G.). Asymptomatic benign M.G. have been detected in increasing numbers during the last decade due to use of cellulose acetate electrophoresis for the routine examination of patients or in the course of systemic screening in normal populations such as blood donors. At the present time, a malignant origin of M.G. cannot be proved in more than thirty per cent of case and these "asymptomatic M.G." must be follow-up by a yearly clinical, hematological and electrophoretical check-up in order to detect a possible malignant evolution. In other cases, M.G. can be associated with neoplasms of cells types not known to produce M-Ig, in cold chronic agglutinin disease, and during the course of some auto-immune disorders.
Total serum proteins were evaluated and serum protein electrophoresis performed on 3 500 blood donors after plasmapheresis. The results were standard for total serum proteins, serum albumin and immunoglobulin in 98% of the donors, whereas monoclonal immunoglobulin, immunodeficiencies or polyclonal hypergammaglobulinemia were detected in 2% of them. The frequency of monoclonal components is roughly 0.3%, corresponding to the frequency observed in normal adults of 40 to 60 years old. Donors found with monoclonal immunoglobulins or immunodeficiency should not be considered as eligible for blood donation.
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Previous studies showed that polyclonal anti-DNA antibodies from patients with systemic lupus erythematosus (SLE) share cross-reactive idiotypes (CRI). In this report, we used human myeloma proteins (HMP), isolated from the serum of patients with multiple myeloma or Waldenström macroglobulinemia, as probes to further explore this idiotypic cross-reactivity. Fourty-four HMP were tested for DNA-binding capacity and for expression of CRI associated with lupus anti-DNA antibodies. Anti-DNA IgG were immunoaffinity purified from the serum of patient TOF with severe SLE. A xenogeneic anti-idiotype antibody to this IgG was raised in rabbit. This anti-idiotype recognized CRI associated with the combining site of anti-DNA IgG from unrelated SLE patients. Using inhibition competitive-immunoassays, we found that these CRI were present on all but one of the DNA-binding HMP. Furthermore, we observed that these CRI were detectable on an IgG2 lambda, a HMP devoid of anti-DNA activity. These findings are in agreement with those previously obtained in similar studies using murine monoclonal anti-DNA antibodies. These converging results suggest that antibodies expressing anti-DNA-related CRI and antibodies exhibiting anti-DNA-binding affinity constitute overlapping molecular subpopulations.
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