Warren M. Gold

Bio: Warren M. Gold is an academic researcher from University of California, San Francisco. The author has contributed to research in topics: Histamine & Mast cell. The author has an hindex of 32, co-authored 99 publications receiving 3114 citations. Previous affiliations of Warren M. Gold include Boehringer Ingelheim & University of California, Berkeley.

Mast cell tryptase causes airway smooth muscle hyperresponsiveness in dogs.

Abstract: Supernatants obtained by degranulation of dog mastocytoma cells greatly increased the sensitivity and the magnitude of the contractile response of isolated dog bronchial smooth muscle to histamine. The enhanced contractile response was reversed completely by H1-receptor antagonists and was prevented by an inhibitor of tryptase (a major protease released with histamine from secretory granules of mast cells). The potentiation of histamine-induced contractions was reproduced by active tryptase in pure form. The contractions due to the combination of histamine and purified tryptase were abolished by the Ca2+ channel blockers nifedipine and verapamil. The bronchoconstricting effects of KCl and serotonin, which, like histamine, contract airway smooth muscle by a mechanism predominantly involving membrane potential-dependent Ca2+ transport, were also potentiated by tryptase. However, the contractile effects of acetylcholine, which contracts dog airway smooth muscle by a mechanism independent of Ca2+ channels, were unaffected by tryptase. These findings show a striking promotion of agonist-induced bronchial smooth muscle contraction by mast cell tryptase, via direct or indirect effects on Ca2+ channels, and the findings therefore suggest a novel potential mechanism of hyperresponsiveness in dog bronchi.

Oxygen may improve dyspnea and endurance in patients with chronic obstructive pulmonary disease and only mild hypoxemia.

Abstract: Oxygen (O2) has been reported to improve exercise tolerance in some patients with chronic obstructive pulmonary disease (COPD) despite only mild resting hypoxemia (PaO2 > 60 mm Hg). To confirm these prior studies and evaluate potential mechanisms of benefit, we measured dyspnea scores by numeric rating scale during cycle ergometry endurance testing and correlated the severity of dyspnea with right ventricular systolic pressure (RVSP) measured by Doppler echocardiography during a separate supine incremental exercise test. Both sets of exercise were performed according to a randomized double-blind crossover protocol in which patients breathed compressed air or 40% O2. We studied 12 patients with severe COPD (FEV1 0.89 ± 0.09 L [mean ± SEM], FEV1/FVC 37 ± 2%, DlCO 9.8 ± 1.5 ml/min/mm Hg [47% of predicted], PaO2 71 ± 2.6 mm Hg). With endurance testing on compressed air, PaO2 did not change significantly in the group as whole (postexercise PaO2 63 ± 5.1 mm Hg, p = NS), but did fall to less than 55 mm Hg in fou...

Alterations in human leukocyte function induced by ingestion of eicosapentaenoic acid

Abstract: Two groups of six adults with persistent asthma, who were identical clinically, received 0.1 or 4 g of purified eicosapentaenoic acid ethyl ester (EPA) daily for 8 weeks. Both doses increased significantly the generation of leukotriene B5 (LTB5) from EPA by polymorphonuclear (PMN) and mononuclear leukocytes, while only the high dose decreased leukocyte arachidonic acid (AA) and the generation of LTB4 and prostaglandin E2 from AA. Only the high dose led to inhibition of PMN leukocyte chemotaxis to multiple stimuli by a mean of 57–70% (P<0.01), without altering monocyte chemotaxis, the production of plateletactivating factor by mononuclear leukocytes, or the IgE-dependent release of histamine from basophils. Both doses of EPA increased the responses of T lymphocytes to phytohemagglutinin by a mean of 73% or more (P<0.01) without modifying the numbers of helper and suppressor T lymphocytes. EPA affects the functions of several types of leukocytes critical to inflammation and immunity.

Physiologic Diagnosis of Subclinical Emphysema

Abstract: The present study was designed to determine whether screening pulmonary function tests could establish a diagnosis of emphysema that was clinically unsuspected in patients undergoing thoracotomy for a localized surgical problem. Seven patients had significantly reduced single-breath diffusing capacity for carbon monoxide (36 to 69 per cent of predicted) and abnormalities in maximal expiratory flow-volume curves, especially at small lung volumes. Maximal expiratory flow was only slightly reduced at 20 per cent of total vital capacity exhaled (57 to 90 per cent of predicted), but was markedly reduced (17 to 46 per cent of predicted) at 80 per cent of total vital capacity exhaled. Despite these physiologic abnormalities, all patients had normal or questionably abnormal values for vital capacity, total lung capacity, forced expiratory volume in one second, and airway resistance. Anatomic studies of lobes or lungs removed within a week after physiologic studies revealed diffuse emphysema in these 7 patients. T...

Antigen-induced airway hyperresponsiveness and pulmonary inflammation in allergic dogs

Abstract: We studied whether antigen-induced airway hyperresponsiveness was associated with pulmonary inflammation in 11 anesthetized ragweed-sensitized dogs. Airway responsiveness to acetylcholine aerosol was determined before and at 2, 6, and 24 h after ragweed or sham aerosol challenge. Pulmonary inflammation was assessed by bronchoalveolar lavage (BAL) performed at either 2 or 6 h. Total pulmonary resistance increased 11-fold at 5 min after ragweed. Airway responsiveness was unchanged at 2 h but was increased 6.6-fold at 6 h in 8 of 11 dogs (P less than 0.001); hyperresponsiveness persisted from 4 days to 4 mo. Airway responsiveness was unchanged by aerosols of diluent. Neutrophils in BAL fluid increased approximately sixfold at 2 h (P less than 0.02) and at 6 h (P less than 0.02) after antigen challenge. There were fewer eosinophils in fluid recovered at 6 h after antigen compared with 2 h lavages (P less than 0.05). In three nonresponders, BAL showed no significant changes in neutrophils and eosinophils after antigen. Thus antigen-induced hyperresponsiveness is associated with the presence of pulmonary inflammation, presumably arising from the airways and involving both neutrophils and eosinophils.

Standards for the Diagnosis and Care of Patients with Chronic Obstructive Pulmonary Disease

Abstract: SUMMARY OF APPROACH The approach to surgery in the patient with COPD is summa-rized below. Surgery Definitely indicated Lung resection. Pulmonary function studies should be performedbefore lung resection. Simple spirometry has the greatest utilityin documenting physiologic operability. FEV, > 2 L in an adultman or > 60% of predicted is acceptable for pneumonectomy.Values below this suggest that further studies, such as split func-tion assessment by quantitative lung scintigraphy and exercisetesting, are warranted.FEV, predicted after lung resection to be less than 40 to 50%of normal for the patient’s sex, age, and height suggests highermorbidity and mortality. An exercise 90, of less than 10 to 15ml/min per kg of body weight is associated with higher mor-bidity and mortality after lung resection.All elective surgery Prophylaxis against deep venous throm-bosis should be given before most procedures that will requirepostoperative bed rest or significantly reduce mobility. Heparinin low doses seems well accepted for most procedures. Externalpneumatic compression of the lower legs can be used when anti-coagulants are contraindicated.