Mechanisms of airway hypercontractility in basenji-greyhound dogs

The comparative effects of contractile agonists and physiological stimulation of the tracheal and bronchial smooth muscle (BSM) response were studied isometrically in situ in five Basenji-greyhound (BG) and six mongrel dogs. Frequency-response curves generated by bilateral stimulation of the vagus nerves (0-20 Hz, 15-20 V, 2-ms duration) elicited greater maximal contraction in mongrel trachea (36.8 +/- 8.1 vs. 26.9 +/- 4.0 g/cm; P less than 0.02) and exhibited greater responsiveness in mongrel BSM (half-maximal response to electrical stimulation 3.0 +/- 1.1 vs. 7.0 +/- 0.5 Hz; P less than 0.05) compared with BG dogs. However, muscarinic sensitivity to intravenous methacholine (MCh) was substantially greater in BG dogs; MCh caused contraction greater than 1.5 g/cm at a mean dose of 3.0 X 10(-10) mol/kg for BG dogs compared with 5.1 X 10(-9) mol/kg for mongrel controls (P less than 0.03, Mann-Whitney rank-sum test). In contrast to the muscarinic response, the contractile response elicited by intravenous norepinephrine after beta-adrenergic blockade was similar in trachea and bronchus for both mongrel and BG dogs. Our data confirm previous in vitro demonstration of tracheal hyporesponsiveness in BG dogs and demonstrate that the contraction resulting from efferent parasympathetic stimulation is less in the BG than mongrel dogs. However, postsynaptic muscarinic responsiveness of BG BSM is substantially increased. We conclude that a component of airway responsiveness in BG dogs depends directly on contractile forces generated postsynaptically that are nongeometry dependent, postjunctional, and agonist specific.     

Effect of resting smooth muscle length on contractile response in resistance airways

We studied the effect of resting smooth muscle length on the contractile response of the major resistance airways (generations 0-5) in 18 mongrel dogs in vivo using tantalum bronchography. Dose-response curves to 10(-10) to 10(-7) mol/kg methacholine (MCh) were generated [at functional residual capacity (FRC)] by repeated intravenous bolus administration using tantalum bronchography after each dose. Airway constriction varied substantially with dose-equivalent stimulation and varied sequentially from trachea (8.8 +/- 2.2% change in airway diam) to fifth-generation bronchus (49.8 +/- 3.0%; P less than 0.001). Length-tension curves were generated for each airway to determine the airway diameter (i.e., resting in situ smooth muscle length) at which maximal constriction was elicited using bolus intravenous injection of 10(-8) mol/kg MCh. A Frank-Starling relationship was obtained for each airway; the transpulmonary pressure at which maximal constriction was elicited increased progressively from 2.50 +/- 1.12 cmH2O for trachea (approximately FRC) to 18.3 +/- 1.05 cmH2O for fifth-generation airways (approximately 50% TLC) (P less than 0.001). A similar relationship was obtained when change in airway diameter was plotted as a function of airway radius. We demonstrate substantial heterogeneity in the lung volumes at which maximal constriction is elicited and in distribution of parasympathomimetic constriction within the first few generations of resistance bronchi. Our data also suggest that lung hyperinflation may lead to augmented airway contractile responses by shifting resting smooth muscle length toward optimum resting smooth muscle length.     

Long-acting contraceptive agents: Norethisterone esters of arylcarboxylic acids

The synthesis of esters of norethisterone (17α-ethynyl-17β-hydroxy-estr-4-en-3-one) with acids containing a benzene ring is described, two methods of esterification being compared in terms of yield and convenience. The activities of these esters as long-acting contraceptive agents have been evaluated.     

Long-acting contraceptive agents: norethisterone esters of monoalkenyl and monoalkynyl acids

The synthesis of nine new esters of norethisterone (17 alpha-ethynyl-17 beta-hydroxyestr-4-en-3-one) is described, with the esterifying acids bearing an acetylenic or olefinic function in a chain of eight or nine carbon atoms, for evaluation as long-acting contraceptive agents.     

The steroids and fatty acids of the basidiomycete Scleroderma polyrhizum

The fruit bodies of the Basidiomycete Scleroderma polyrhizum have been shown to contain the steroids ergosta-4,6,8(14) 22-tetraen-3-one and 5α,8α-epidoxyergosta-6,22-dien-3β-ol and also palmitic and oleic acids.     

Immunopathology of murine experimental allergic orchitis

Experimental allergic orchitis (EAO) was induced consistently in BALB/c mice by immunization with homologous testicular tissue homogenate emulsified in complete Freund's adjuvant (CFA) providing that the animals had received simultaneously at least 1 microgram of an extract of Bordetella pertussis rich in pertussigen. All animals thus treated developed orchitis and serum antibody to testicular antigens within 20 days after immunization. The lesions were located in testis (100%), rete testis (37%), cauda epididymis (21%), and vas deferens (37%). Ductus efferentes and caput epididymis were only rarely affected. Early lesions in the seminiferous tubules were characterized by peritubular and/or intratubular accumulation of eosinophils, neutrophils, lymphocytes, and macrophages. This was followed by aspermatogenesis. Late lesions included massive necrosis and extensive fibrosis of the seminiferous tubules. Disruption of blood-testis barrier on day 20 was evidenced by the detection of 1) perfused lanthanum deposits between Sertoli cells and surrounding inflammatory cells inside the seminiferous tubules, 2) deposits of endogenous mouse IgG in germinal epithelium, and 3) probable immune complexes (granular C3) surrounding seminiferous tubules. Murine EAO differed from that of the guinea pig in the lack of involvement of the ductus efferentes, the extensive necrosis, the abundant polymorphonuclear eosinophils in the lesion, and the exquisite requirement of concomitant injection of B. pertussis extract.     

Modulation of the biologic activities of IgE-binding factor. II. Physicochemical properties and cell sources of glycosylation-enhancing factor

T lymphocytes of rats treated with Bordetella pertussis vaccine (BP) formed a soluble factor that enhanced the glycosylation of IgE-binding factors during their biosynthesis, and provided the latter factors with the biologic activity to potentiate the IgE response. The present experiments demonstrated that pertussigen (leukocytosis-promoting factor) from BP induced normal rat spleen cells to form the glycosylation-enhancing factor. The same factor was obtained by incubation of normal spleen cells with 5 micrograms/ml, but not 2 micrograms/ml, concanavalin A. When normal rat mesenteric lymph node cells were incubated with the glycosylation-enhancing factor together with IgE, IgE-binding factors formed by the cells selectively potentiated the IgE response. The IgE-binding factors formed by the same cells upon incubation with IgE alone neither enhanced nor suppressed the IgE response. The glycosylation-enhancing factor changed the nature of IgE-binding factors formed by the rat-mouse T cell hybridoma, 23A4. IgE-binding factors induced by IgE alone lacked affinity for lentil lectin, whereas those induced by IgE in the presence of the glycosylation-enhancing factor had affinity for the lectin. The cell source of the glycosylation-enhancing factor appeared to be W 3/25+ Fc gamma R+ T cells. The glycosylation-enhancing factor was protein in nature and had a m.w. of about 25,000. The factor had affinity for acid-treated Sepharose and could be recovered from the beads by elution with lactose. The factor was different from interleukin 2 with respect to both its affinity for galactose and its isoelectric point.     

Passive Cutaneous Anaphylaxis with Antigens from Coxiella burneti

Passive cutaneous anaphylaxis (PCA) was produced in guinea pigs sensitized with guinea pig Coxiella burneti phase I–II antiserum and challenged with dimethylsulfoxide- or trichloroacetic acid-soluble extracts from phase I cells. The PCA reaction could not be induced by whole or mechanically disrupted phase I or phase II C. burneti cells or by extracted cells or extracts of phase II cells. The antibody responsible for PCA was in the 7Sγ₁ (fast γ) globulin. Sensitization of the skin by 7Sγ₁ antibody could be blocked nonspecifically by 7Sγ₁ globulin from normal serum or from phase II antiserum. The 7Sγ₂ (slow γ) globulin antibody inhibited the reaction specifically. Some antiserum pools containing high agglutinin and complement-fixing titers to phase I C. burneti cells failed to initiate the PCA reaction, perhaps due to an imbalanced ratio of γ₁ to γ₂ specific globulins or to an imbalance in the ratio of specific to nonspecific γ₁ globulins. Agglutinins to phase I cells were found in both γ₁ and γ₂ antibody globulins. Complement-fixing antibodies were found in the γ₂ globulin fraction.