Togo Ikeda

Respiratory involvement in polychlorinated biphenyls poisoning

Abstract Clinical, laboratory, and pathological findings on respiratory involvement in polychlorinated biphenyl (PCB) poisoning were studied in 401 patients and their pathological changes were produced in rats given PCBs orally. Respiratory symptoms included expectoration in 40% of the 289 nonsmoking patients with PCB poisoning and mild wheezing in 2%. The incidence and severity of the respiratory symptoms correlated well with the concentration of PCBs in the blood and sputa. Chest roentgenographic findings, pulmonary function tests, and pathological findings revealed bronchiolitis in many, and pneumonia or atelectasis in about one-tenth of the patients with reticulo-linear shadows. Peribronchiolar changes may be primarily due to either PCB poisoning or associated infection. Respiratory distress was often exacerbated by viral or bacterial infection persisting for more than a half year in about half of the patients examined. The IgA and IgM levels in the serum decreased considerably within 2 years after the onset of the disease and definite decreases in IgA levels may correlate well with the bacterial infection. PCBs found in sputa may have been present in association with lipid in type II cells of the lung (or with excretion from bronchial cells) and may have been phagocytosed in alveolar macrophages and may change their phagocytic function.

Effects of Procaterol, a Beta-2-Adrenoceptor Stimulant, on Neuroeffector Transmission in Human Bronchial Tissue

It has been reported that low concentrations of noradrenaline or isoprenaline reduce the resting tension of the smooth muscle cells and suppress acetylcholine release from the vagal nerve terminals through activation of beta 2-adrenoceptors. Procaterol, beta 2-adrenoceptor stimulant, has a high potency and selectivity for airway smooth muscle tissues. However, there is little documentation on the prejunctional actions of this chemical in airway smooth muscle, especially in man. In the present study, the effects of procaterol on excitatory neuroeffector transmission in the human bronchus were investigated. Procaterol (10(-10) to 10(-7) M) dose dependently reduced the amplitude of the contractions evoked by electrical field stimulation in the presence of indomethacin (10(-5) M), FPL-55712 (10(-6) M), and guanethidine (10(-6) M). By contrast, procaterol (10(-10) to 10(-9) M) had no effect on the postjunctional response of smooth muscle cells to exogenously applied acetylcholine. Pretreatment with ICI-118551 (10(-7) M), a beta 2-adrenoceptor-blocking agent, reduced the inhibitory action of procaterol on the amplitude of twitch contractions evoked by field stimulations in the human bronchus. These results indicate that procaterol at low concentrations has a prejunctional action, inhibiting the excitatory neuroeffector transmission and presumably suppressing transmitter release from the vagal nerve terminals through beta 2-adrenoceptors in the human bronchial tissue. The prejunctional action of procaterol explains partly its potent bronchodilator effects in clinical use.

The changing pattern of lung cancer by histological type — a review of 1151 cases from a university hospital in Japan, 1970–1989

We have analysed the frequency distribution and incidence rates for each histological type of newly diagnosed lung cancer in 1151 cases seen from 1970 through 1989 at Kyushu University, Japan. The incidence of adenocarcinoma has increased significantly since 1970. The proportion of adenocarcinoma increased from 26% to 45% in males (P<0.0001) and from 45% to 69% in females (P=0.0002). In addition, the proportion of subtypes of adenocarcinoma, classified in an electron microscopic study, underwent marked changes during the period 1982–1985; thus, e.g. 71% of all adenocarcinomas were classified as being of the bronchiolo-alveolar type. The smoking rates were similar during the period for patients with adenocarcinoma, suggesting that some etiological factors other than smoking may account for the increased incidence of adenocarcinoma. Further analysis, especially respecting dietary or ecological factors, is necessary.

Effect of Endogenous Tachykinins on Neuro-Effector Transmission of Vagal Nerve in Guinea-Pig Tracheal Tissue

To elucidate the effect of endogenous tachykinins on neuro-effector transmission of vagal nerves, we performed in vitro experiments using guinea-pig tracheal smooth muscle. The subthreshold dose (the highest dose which did not induce any smooth muscle contraction) of capsaicin (10(-8) to 10(-7) M) increased the amplitudes of contractions evoked by electrical field stimulation (EFS) significantly, but not those by acetylcholine (ACh). The inhibitor of neutral endopeptidase, phosphoramidon (10(-7) to 10(-6) M), increased the contractions evoked by EFS significantly. The inhibitor of cholinesterase, physostigmine (10(-6) to 10(-5) M), induced smooth muscle contractions, but such contractions were inhibited by atropine, suggesting the spontaneous release of ACh from the vagal nerve terminals. The subthreshold dose of substance P or capsaicin increased the contractions evoked by physostigmine. These results indicated that endogenous tachykinins increase the spontaneous ACh release as well as the ACh release in response to vagal stimulation from the nerve terminals. Furthermore, it is suggested that the excitatory effects of the tachykinins on the vagal neuro-effector transmission may be modulated by neutral endopeptidase in the guinea pig.

Herpes Zoster in Patients with Sarcoidosis

108 patients with sarcoidosis were retrospectively studied for the development of herpes zoster. Five of these patients (4.6%), 2 of whom were in their twenties, developed herpes zoster. Only 1 patient had been treated with an oral steroid. All 5 had extrathoracic lesions. Zoster tended to occur during the inactive stage of sarcoidosis and did not exacerbate the activity of the sarcoidosis. The clinical course of their zoster infection was typically benign. There have been few reports of herpes zoster in patients with sarcoidosis. Further studies are required to determine whether sarcoidosis predisposes to herpes zoster infection.

Protective effect of a thromboxane synthetase inhibitor, OKY-1581, on increased lung vascular permeability in pulmonary microembolization in dogs

To evaluate the potential beneficial effect of a thromboxane synthetase inhibitor, OKY-1581, on increased pulmonary vascular permeability in pulmonary microembolization, we have measured the filtration coefficient in the nonembolized lung after unilateral microembolization in dogs. The unilateral microembolization caused marked elevations in pulmonary artery pressure and blood flow to the nonembolized lung, while pulmonary venous pressure in nonembolized lung did not change. The pulmonary vascular resistance in nonembolized lung did not increase significantly. The filtration coefficient (Kf) in nonembolized lung increased to 0.14 +/- 0.02 from the baseline value of 0.07 +/- 0.01 ml/min/mmHg/100g at 30 min after microembolization when the initial hemodynamic changes reduced toward the baseline value. In OKY-1581 treated dogs, similar hemodynamic changes did not result in the increase in the filtration coefficient in nonembolized lung. Platelet aggregation was also inhibited after microembolization in OKY-1581 treated dogs. Based on these results, we could conclude that OKY-1581 could prevent the increase in pulmonary vascular permeability following pulmonary microembolization by inhibiting platelet aggregation and possibly by preventing the release of thromboxane A2.

A pathophysiological role of endogenous prostacyclin in endotoxin induced increase in lung vascular permeability in dogs

Escherichia coli endotoxin (1 mg/kg) infusion over 30 min into anesthetized artificially ventilated dogs caused a biphasic response: an early phase of pulmonary hypertension and a late phase of increased lung vascular permeability. During an early phase, PG F2 alpha, Tx A2 (as Tx B2) and prostacyclin (as 6-keto-PG F1 alpha) concentrations increased in plasma or right duct lymph of dogs. During a late phase, the concentrations of PG F2 alpha and Tx A2 decreased to near the base-line values, while the concentration of prostacyclin remained elevated. Administrations of PG synthetase inhibitors 45 min prior to endotoxin inhibited the increase in concentration of prostacyclin following the infusion of endotoxin and potentiated the increase in lung vascular permeability at the beginning of the late phase. Continuous infusion of prostacyclin (20 ng/kg/min) starting one hour before endotoxin for 5 hour periods prevented the increase in lung vascular permeability induced by endotoxin. Based on these results, we could conclude that endogenous prostacyclin might play an important role in preserving cell integrity of lungs and counteract the deleterious effects of endotoxin.

The effect of prostacyclin on increased hydraulic conductivity of pulmonary exchange vessels following microembolization in dogs

Prostacyclin (PG I2) generated by vascular endothelium is a strong antiaggregating substance. As platelet aggregation and release of humoral factor(s) have been reported to be crucial in the pathogenesis of acute lung injury following pulmonary microembolization, PG I2 could have a protective effect against microembolic lung vascular injury. Following unilateral microembolization, we have observed a large increase in the filtration coefficient in the nonembolized lung with a significant increase in 6-keto PG F1 alpha, the stable metabolite of PG I2, in arterial blood. The pretreatment with indomethacin (10 mg/kg) prevented the increase in 6-keto PG F1 alpha and potentiated the lung injury after microembolization. Exogenously administered PG I2 (20 ng/kg/min) prevented completely the increase in the filtration coefficient without any effects on hemodynamics, although these effects of indomethacin and PG I2 did not relate to their effects on platelet aggregation. Based on these results, we could conclude that prostacyclin could play an important role in preserving cell integrity of the lung and in prevention of increased lung vascular permeability following pulmonary microembolization.

The effect of prostacyclin infusion on increased pulmonary vascular permeability following microembolization in dogs

Prostacyclin (PG I2) generated by vascular endothelium is a strong antiaggregating substance. As platelet aggregation and release of humoral factor(s) have been reported to be crucial in the pathogenesis of acute lung injury following pulmonary microembolization, prostacyclin could have a protective effect against microembolic lung vascular injury. Following unilateral microembolization, the filtration coefficient in the nonembolized lung increased significantly to 0.14 +/- 0.02 from the base line value of 0.07 +/- 0.01 ml/min/mmHg/100g. Prostacyclin as measured as 6-keto PG F1 alpha in arterial blood increased significantly to 4.15 +/- 1.76 at 30 min from the base line value of 1.90 +/- 0.45 ng/ml and increased further to 5.67 +/- 1.49 ng/ml at 60 min following microembolization. Exogenously administered PG I2 methylester (20 ng/kg/min) prevented completely the increase in the filtration coefficient without any effects on hemodynamics, although the effects of PG I2 methylester did not depend on its action on platelet aggregation. Based on these results, we conclude that prostacyclin could play an important role in preserving cell integrity of the lung and prevention of increased lung vascular permeability following pulmonary microembolization.