Human respiratory mucus.
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Biomedical subjects
Publications and source records attributed to J Shelhamer.
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In order to examine the mechanisms by which corticosteroids may benefit some patients with bronchorrhea, cultured human airways releasing [3H]glucosamine labeled mucous glycoproteins were exposed to corticosteroids, and mucus release was examined. Both dexamethasone and methylprednisolone produced dose-related suppression of the spontaneous release of radiolabeled mucous glycoproteins. The inhibitory effects of dexamethasone were maximal after 18 to 24 h and returned to control levels by 34 h. In order to study the effects of dexamethasone on stimulated mucus release, airways were exposed to dexamethasone and to the mucus secretagogues, histamine or 5-monohydroxyeicosatetraenoic acid. Both of these secretagogues stimulated radiolabeled mucous glycoprotein release from airways that had never been exposed to corticosteroids, as well as in a reduced fashion from corticosteroid-treated airways. The reduced mucus release caused by secretagogues from dexamethasone-treated airways appeared to reflect a lowered baseline secretion rate rather than a specific inhibition of either secretagogue.
To assess the sensitivity of bronchoalveolar lavage in patients with the acquired immunodeficiency syndrome (AIDS) in diagnosing Pneumocystis carinii pneumonia (PCP), we prospectively performed 27 bronchoalveolar lavages (BAL) in 16 patients either because there was an initially high index of suspicion of PCP or in order to assess therapeutic response to anti-Pneumocystis medication in those patients who had had PCP documented. Pneumocystis organisms were demonstrated on BAL specimens in 16 of 18 procedures in patients with histologic evidence of PCP on simultaneously obtained pulmonary tissue. The diagnosis was established rapidly by BAL and there was no substantial morbidity attributable to the procedure. Subsegmental BAL may be an important and sensitive tool for early diagnosis of PCP in patients with AIDS.
An in vitro system of human nasal turbinate tissue culture has been developed. Nasal turbinate tissue resected during surgery for nasal obstruction is dissected free of bone, placed on absorbable gelatin sponges, and cultured with CMRL-1066 medium containing antibiotics. Viability of explants may be demonstrated both physiologically and histologically through a period of 4 weeks. 3H-glucosamine added to the medium is biosynthetically incorporated into mucous glycoprotein (MGP). Gel filtration column chromatography on Sephacryl S-1000 in 6M urea in 0.005M phosphate buffer demonstrates human turbinate MGP to fractionate with 85% of the radiolabel filtered and 15% excluded by the column. The excluded MGP fractionates with globular proteins of greater than 20 X 10(6) daltons, while the fractions that enter the column filter with molecular sizes of 0.4 X 10(6) to 20 X 10(6) daltons. MGP synthesized by human lung airways has comparable sizing characteristics, suggesting a similarity in upper and lower airway mucus chemistry.
Clinical features of 49 episodes of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome were compared with those of 39 episodes in patients with other immunosuppressive diseases. At presentation patients with the syndrome were found to have a longer median duration of symptoms (28 days versus 5 days, p = 0.0001), lower mean respiratory rate (23.4 versus 30, p = 0.005), and higher median room air arterial oxygen tension (69 mm Hg versus 52 mm Hg, p = 0.0002). The survival rate from 1979 to 1983 was similar for the two groups (57% and 50% respectively). Patients with the syndrome had a higher incidence of adverse reactions to trimethoprim-sulfamethoxazole (22 of 34 versus 2 of 17, p = 0.0007). Survivors with the syndrome at initial presentation had a significantly lower respiratory rate, and higher room air arterial oxygen tension, lymphocyte count, and serum albumin level compared to nonsurvivors. Pneumocystis carinii pneumonia presents as a more insidious disease process in patients with the syndrome, and drug therapy in these patients is complicated by frequent adverse reactions.
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The diagnosis of Pneumocystis carinii pneumonia conventionally depends on the time-consuming demonstration of the organisms in pulmonary secretions or lung tissue using toluidine blue 0, methenamine silver, or Gram Weigert stains that require special reagents. In 27 recent episodes of moderate to heavy pneumocystis infections, the cyst form and internal sporozoites of P. carinii could be readily identified on lung imprints using the conventional Gram stain. The Gram stain is unlikely to replace special stains for the diagnosis of pneumocystosis, but it does provide a rapid method to recognize moderate to heavy infections.
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Human nasal turbinates were cultured in the presence of 3H-glucosamine, which is incorporated into nasal mucous glycoproteins. Nasal mucous glycoprotein was then characterized biochemically, and the effects of various neurohormones and immunologic stimulation on mucous glycoprotein release were analyzed. Fractionation of nasal mucous glycoprotein by gel filtration chromatography revealed a molecular size range of 2 to 200 X 10(5) (as judged by protein markers) but displayed a single, acidic charge, as reflected both in a narrow elution pattern from DEAE-cellulose and a sharp isoelectric focusing point of 2.6. Highly enriched nasal mucous glycoprotein preparations consisted of 80 per cent carbohydrate and 20 per cent protein (by weight) and included enzymatically cleavable carbohydrate side chains with molecular weights of 1,600 to 1,800. Thus, nasal mucous glycoproteins are a family of molecules that express uniform acidic charge characteristics and a wide range of molecular sizes. Cholinergic stimulation of atropine-inhibitable muscarinic receptors increased nasal mucous glycoprotein release in a dose-related manner, as did alpha-adrenergic stimulation. However, beta-adrenergic stimulation did not affect mucous glycoprotein release. Immunologic stimulation of nasal mast cells by either reversed anaphylaxis or antigen challenge after passive sensitization caused both histamine release and increased mucous glycoprotein release. Thus, nasal turbinates provide an accessible source of tissue for the analysis of nasal mucus secretion and mast cell degranulation and may provide a model for the study of pharmacologic approaches to the universally experienced discomfort of rhinorrhea.
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