Clinical and experimental studies on pulmonary lesions due to circulatory disturbances, both acute and chronic forms as represented by ARDS and hepatogenic cyanosis revealed the following results: with regard to ARDS, our studies on 33 clinical cases suggested the presence of two different types in this syndrome according to etiology; while the transient abnormalities in ventilation and circulation are involved in the one, general cytotoxic effects could be one of the causative factors in the other. A careful differential diagnosis of ARDS from pulmonary embolism should be made since the symptoms of pulmonary embolism is similar to ARDS. A common histopathological finding among these three types of pulmonary circulatory diseases is pulmonary edema, especially prominent changes in perivascular space.
Contrary to the rather fair prognosis in the type of ARDS caused by ventilation-perfusion disorders, that of cytotoxic origin is poor as reflected by quality and quantity of extravascular lung fluid.
Further, in the latter type both microscopic and electron microscopic findings of lung tissue showed vast tissue damage including pulmonary vasculature and one of the clinical manifestations was low cardiac output.
On the basis of free radical theory, a study using paraquat lung edema was attempted and we confirmed that α-tocopherol in large dose had an inhibitory effect on damage to cellular membrane by cytotoxic factors but no evidence of such effect was obtained with superoxide dismutase.
The validity of measurement of closing volume and double indicator dilution method for indirect measurement of lung water was examined. The measurement of closing volume is likely to be useful for the detection of edema in early clinical stage since this showed a rise in the initial stage and a decrease in the later stages. Measurement of cardiac output using single as well as double indicator is a valid method for predicting prognosis of ARDS.
Although there still are some grounds for hesitating to accept ARDS as a clinical entity and skepticism to use the term to describe the clinical situation among many workers, the term could be used if appropriate specification of the causative agent is added since therapeutic measures are different for different etiologles.
With regard to hepatogenic cyanosis, it is unlikely that a single mechanism such as intrapulmonary microshunt is involved as a causative factor except in the case of juvenile type liver cirrhosis, and one must take into account a multitude of factors such as thoracic and abdominal lesions associated with liver cirrhosis affecting the pulmonary gas exchange. Hypertrophy of medium and small sized pulmonary arterles, was demonstrated in about 30% of cirrhotic patients by autopsy. However the pathogenesis of pulmonary arterial lesions is different from that of primary pulmonary hypertension and pathological changes of pulmonary vasculature in liver cirrhosis may be due to intrapulmonary complications or chronic hypoxic stimuli.

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As Biosystems interact with many kinds of characterized subsystems in the body, systems therory would be useful for analysis of a complex living system. This paper deals with the application of systems theory to lung mechanics, showing a few examples studied in our laboratory.
1) The peripheral airways contribute little resistance to flow. If half the small airways were to be obstructed, resistance at this level would double but the total airway resistance would only increase 10%, which is the reason for calling the small airways region a silent zone. But, it was clarified by systems analysis for a bronchial tree that this simple estimation must be changed. The total resistance of the ventilatory system varied with different distributions of obstructed small airways, even when the total number was equal.
2) In an analog simulation of an 8-compartment model for uneven ventilation, it was observed that the disorder of one compartment affects the ventilation of not only that compartment but also other compartments adjacent to it.
3) Gas streaming between alveoli, Pendelluft, was analyzed quantitatively by the 8-compartment model. The amplitude of Pendelluft increases with decreased time constant as the distance from the disorder compartment decreases.
4) It has been recognized that the performance criterion of the respiratory rate is determined as the minimum of either the energy of ventilation or the average muscle force under varying environmental conditions. Such performance criterion obtained from the linear analysis of a ventilatory system was contradicted partly by our experimental data which showed a non-linear oscillation system within some variation of airway resistance.
5) A dual control system for assisting respiration was developed by the systems analysis of complex man-machine systems. This system is capable of maintaining both the arterial PCO₂ and PO₂ within normal levels at any level of metabolic rate or any respiratory frequency.

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An autopsied case of multiple micro-bone formation in the lung of a patient (74 year-old, male) with diffuse interstitial pneumonia was presented. About a year passed from the onset of the disease to death. The honeycomb appearance was noted on the cut surfaces of both lower lobes. Advanced fibrosis and destruction of the lung were marked histopathologically. Numerous micro-bones with bone marrow were seen in alveolar spaces of both lungs, particularly of the right mid and lower lobes. The bones were too small to be seen radiologically. Cardiac abnormality was not detected. The mechanism of ectopic bone formation was discussed.

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Alveolar macropahges from rabbits were exposed in culture medium to asbestos, beryllium sulfate and beryllium oxide. The specific activities of the lysosomal hydrolases, acid phosphatase; β-N-acetylglucosaminidase; β-glucuronidase; and glycolytic enzyme, phosphohexose isomerase, were determined in the medium, whole cell homogenates, mitochodrial fractions and in the supernatant. These hydrolases increased significantly in the medium but not in the mitochondrial fraction of cells exposed to dusts. For the induction of enzyme release in vitro, a higher concentration of beryllium oxide than that of the other two dusts was requisite. Very cytotoxic effects on the cells were seen in the culture cell groups of both asbestos and beryllium sulfate.

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The history of a representative case, a 17 year-old female, was as follows: The patient had experienced shortness of breath following exertion since childhood. At the age of 13, a presumptive diagnosis of miliary tuberculosis was made by chest roentgenogram. The next year, a diagnosis of pulmonary malformation was made by histological examination of specimens obtained by open-lung biopsy. From the age of 15, pneumothorax occured repeatedly and she expired from dyspnea.
Autopsy findings of the lungs were as follows: Both right and left were somewhat solid and firm in general, and many cystic cavities of sizes varying from miliar to little finger tip size were noted. Also, numerous small bone particles of rice grain size were scattered throughout both lungs.
Microscopically, the cysts seen in macroscopic view were recognized to be bronchial cysts, lined by ciliated columnar or cuboidal epithelium. Adenomatoid proliferation and dilatation of bronchioles associated with smooth muscle hyperplasia was also noted. Differentiation of alveoli was poor, and underdeveloped alveoli showed emphysematous dilatation and thickening of the walls due to fibrosis and smooth muscle hyperplasia.
Between these bronchiles alveoli and cysts, diffuse or somewhat nodular fibrosis with admixture of smooth muscle was observed. Among these stroma, many small nodules of bone were scattered without connection to the bronchial walls.
The greater parts of the findings in the lungs of present case were coincident with those of “cystic fibrosis of the lung”, called Kurobane meaning an advanced fibrotic form of “musclar cirrhosis of the lung”. However, many scattered small nodules of bone were not emphasized in previous reports of this condition. In the present case, it was interesting that the nodules gave very characteristic features in the chest roentgenogram.

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要約: 72才女性の症例で, 胸部レ線上縦隔洞影の拡大と, 左肺野に多発性の胸膜腫瘤陰影を認めた. 数回の経皮吸引生検. 気管支造影, 気管支鏡検査を行つたが, 生前に確定診断は得られなかつた. 剖検により, この腫瘍はoncocyte型を伴つた気管支力ルシノイドで頓挫型の多発性内分泌腺腫 (甲状腺に2ヶの腺腫及び好酸性腺腫の傾向のある多発性の増殖巣, 左副腎に black adenoma 及び腺腫, 後腹膜に異所性の副腎組織) の合併も認めた.

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