Cytophotometric Feulgen-DNA measurement was carried out on mesothelial cells in 40 pleural effusions (malignant: 20, non-malignant: 20 cases) obtained from 40 autopsy cases. No significant difference was found between the DNA amounts of mesothelial cells in malignant effusion and those in non-malignant effusion.
However, histological examination of the pleura in 40 cases, showed that the DNA amounts of mesothelial cell change according to the inflammatory stage of pleuritis. In the early stage of pleuritis showing pleural edema, slight hemorrhage and infiltration of some inflammatory cells, the mesothelial cells in non-malignant effusion showed a significantly higher DNA value than in malignant effusion. On the contrary, at the stage of fibrofibrinous pleuritis, the former showed a lower DNA value than the latter. In addition, accompanied with the progression of the inflammatory stage of pleuritis, a peculiar alteration of the mesothelial DNA amounts was confirmed in both malignant and non-malignant effusions. The pathogenesis was discussed with regard to such cell kinetics of mesothelial cells in pleural effusions.

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The purpose of this study was to clarify the local immunity and pathological state in sarcoidosis by means of bronchoalveolar-lavage (BAL). Some protein components in lavage fluid from 16 sarcoidosis patients were studied and compared with 10 healthy controls.
The assayed parameters included albumin, IgG, IgM, IgA, total secretory components (SC), β₂-microglobulin (β₂-M), angiotensin converting enzyme (ACE), and lysozyme (LYZ).
The BAL levels of all these proteins were elevated in sarcoidosis, and the levels of IgG, IgA, SC, β₂-M and ACE were increased with statistical significance. Furthermore, these were higher in the active stage than in the inactive stage. Alubumin concentration was correlated to IgG, IgA, β₂-M, ACE and LYZ levels in lavage fluid. The ratios of immunoglobulin to albumin in lavage fluid were increased significantly in sarcoidosis, and the ratios of β₂-M and LYZ also seemed to be increased in sarcoidosis. However the ratios of ACE in sarcoidosis case were no different from those of controls. These results suggested not only an increased serum transdation process but also increased local production of immunoglobulin, β₂-M and LYZ, however, the acceleration of local production of ACE could not be observed.

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Twenty-two patients with primary lung cancer were treated by injecting several anti-cancer drugs directly into intrabronchial tumors through a fiberoptic bronchoscope.
1) When tumors were visible through a fiberoptic bronchoscope, they became reduced in size and the accompanied changes were improved after this therapy.
2) Infiltrative changes in the bronchial membrane were also improved after this therapy.
3) This therapy has no serious complications and is minimally invasive.
4) These results suggest that this therapy might be a useful in the treatment of primary lung cancer.

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As an aid to understand the local immunity and pathological state of sarcoidosis in the lung, we studied the cellular components of broncho-alveolar lavage fluid (BAL) in 16 patients with sarcoidosis and the data were compared with those of 10 healthy controls.
The percentages of lymphocytes, T cells and Tr cells in BAL were increased in sarcoidosis (28.8±23.6%, 84.4±7.7% and 17.7±6.9% respectively) as compared with those in controls (7.6±5.6%, 72.4±10.0% and 2.9±2.1% respectively).
The absolute cell counts of lymphocytes, T cells and Tr cells in BAL were increased in sarcoidosis (1.4±1.4×10⁵/ml, 1.2±1.3×10⁵/ml and 1.6±1.6×10⁴/ml respectively) as compared with those in controls (3.0±2.0×10⁴/ml, 2.0±0.9×10⁴/ml and 1.0±1.0×10³/ml respectively). These tendencies were more remarkable in the active stage than in the inactive stage.
The phagocytic activity and nitroblue tetrazorium (NBT) reduction activity of pulmonary alveolar macrophages (PAM) were more elevated in sarcoidosis than in controls.
It was concluded that lymphocytes, T cells and Tr cells in BAL were increased in number in sarcoidosis and that the functions of pulmonary alveolar macrophages were activated in the disease.

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In 40 patients with malignant pleurisy associated with lung cancer, electrolytes, nitrogen compounds, lipid and enzymes in both pleural fluid and serum were measured to assess the permeability status of the pleural space in disease states.
The concentration ratios of pleural fluid to serum were nearly 1.0 in electrolytes, glucose, urea-N and ceratinine. However, the ratios of the concentration of total protein and immunoglobulins were less than 1.0 and inversely related to their molecular weight. It is suggested that the transfer of solutes into pleural space from vascular space was dependant on the size of the molecular weight.
The concentrations of amylase, bilirubin, carcinoembryonic antigen and lactic dehydrogenase were higher than the values estimated by their molecular weight. These elevations in pleural fluid are presumably attributed to hemolysis, associated inflamation and/or production by tumor cells in pleural fluid.

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Natural Killer (NK) activity was measured by ⁵¹Cr release assay in 33 patients with sarcoidosis and 54 healthy controls. The results were as follows:
1) In the control group, NK activity was independent of the donors' age. NK activity of the male in the control group was higher than that of the female, but statistically not significant.
2) NK activity in patients with sarcoidosis was significantly higher than in the control group, and was higher in the active stage than in the inactive stage.
3) NK activity increased in patients with bilateral hilar lymphadenopathy and/or pulmonary infiltration as compared to patients with no abnormal findings on chest roentgenography.
4) NK activity was suggested to be a useful index to evaluate the disease activity of sarcoidosis.

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The precipitating antibodies to the extracts of 31 environmental antigens detected by gel diffusion in sera from patients with 5 different chronic pulmonary diseases (tuberculosis, pulmonary fibrosis, diffuse panbronchiolitis, bronchial asthma and bronchoectasis) were examined. The contents of immune-complexes in these sera were measured by Cl_q solid phase radioimmunoassay. The results indicate that the diseases with marked roentgenographical findings have more precipitating antibodies and a higher titer of immune-complex. The possibility was considered that environmental antigens may participate in developing or in aggravating such pulmonary diseases.
Precipitating antibodies to some antigens were shown in the sera of nomal subjects, indicating that the detection of precipitating antibodies does not necessarily mean the existence of hypersensitive pneumonitis.
The serum IgE levels in diffuse panbronchiolitis were measured by enzyme immuno assay (EIA) to show that IgE concentration in such patients is within normal limits. Diffuse panbronchiolitis does not seem to have a pathogenesis with a reaginic back ground.

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The chemical mediators involved in the pathogenesis of immediate-type hypersensitivity have been the subject of extensive investigations. Immediate-type 1 hypersensitivity reactions are characterized by the immunologically-induced release of histamine, serotonin, prostaglandins and SRS-A. In the present investigation the effect of various drugs on anaphylactic release of histamine, serotonin and heparin from passively sensitized guinea pig lung tissue was studied.
Male white rabbits weighing 2.7-3.0Kg were sensitized with ovalbumin (O-Alb) and gamma globulin was prepared from their peripheral sera by the salting out method. The lung tissue from male Hartley strain guinea pig was minced into fragments (30-50mg). The lung fragments were divided into 0.5 or 1.0g of replicates, and were incubated in gamma globulin solution at 37°C for 3-4 hours saturated with oxygen and carbon dioxide (95:5, v/v). Histamine, serotonin and heparin released from lung fragments by challenging with O-Alb were measured by the methods of OPT, ninhydrin and Azure-A, respectively.
1) The release of histamine, serotonin and heparin was increased dose-dependently by increasing the dose of O-Alb.
2) The release of histamine, serotonin and heparin was inhibited by preincubating with isoproterenol, prostaglandin E₂, 6-keto PGF_1α, disodium cromoglycate, cyclic AMP and verapamil, while it was accelerated by preincubating with thromboxane B₂ and dibutyryl cyclic GMP.
3) The release of histamine, serotonin and heparin showed a tendency to decrease after preincubation with tranexamic acid.
4) There was no correlation between the wet lung tissue weight and the concentration of 6-keto PGF_1α or thromboxane B₂ in the incubation medium after O-Alb challenge.
5) The release of heparin correlated highly with that of histamine and serotonin.
The above results suggest that the release of heparin may play an important role in the release mechanism of various chemical mediators.

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The pathogenesis of endotoxin shock is still a matter of speculation. There is a discrepancy between the direct action of endotoxin and its indirect action through chemical mediators. In the present investigation we measured plasma levels of 6-keto PGF_1α, thromboxane B₂, histamine and serotonin after intravenous injection of E. Coli endotoxin.
Mongrel dogs, weighing between 20 and 30kg, were anesthetized with intravenous administration of 25mg/kg of sodium pentobarbital. Catheters were inserted into left femoral artery and vein, and measurement of systemic arterial blood pressure (Psyst) and transfusion or infusion of drugs were conducted, respectively. E. Coli endotoxin (1mg/kg) was injected into the femoral vein and blood samples for the assay of plasma histamine, serotonin, 6-keto PGF_1α and thromboxane B₂ (TxB₂) were taken from the catheter inserted into the femoral artery.
1) Plasma 6-keto PGF_1α level reached the maximum 1min. after endotoxin injection, thereafter it showed gradual decrease.
2) Plasma TxB₂ level showed rapid increase and reached a plateau 5min. after endotoxin injection and stayed at almost the same level for 60min..
3) Plasma histamine level showed significant increase and continued to increase 60min. after endotoxin injection.
4) Plasma serotonin level showed rapid decrease and reached a minimum 10min. after endotoxin injection, thereafter it showed a tendency to recover.
5) These changes of plasma 6-keto PGF_1α, TxB₂, histamine and serotonin level were suppressed almost completely by the prior administration of indomethacin.
The above results suggest that various humoral factors may play an important role in the pathogenesis of endotoxin shock.

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About 430 post-mortem examinations performed at the Department of Pathology of Kyorin University between April 1978 and December 1980 were reviewed. Lungs from patients who died of hemorrhage numbered twenty-nine, 11 cases of those were ruptured esophageal varices and 10 were gastric hemorrhage. Microscopically, the vacuole formation of endothelial cells was seen in 34% of the cases, adhesion (or plugging) of leukocytes in venules and capillaries was seen in 72%, bone marrow embolus due to heart massage was seen in 40% and the perivascular edema was observed in 76%. The occurrence of microthrombi was rare compared to other forms of shock.
Hemorrhagic shock in the rabbit was produced by arterial bleeding. Mean arterial blood pressure was maintained at 40-50mmHg for 1.5 hours during blood loss amounting to 3.6-2.3% of body weight. Histologically, the intravascular sticking of leukocytes and perivascular edema occurred in the lung. Electron microscopic examinations showed edematous swelling of the cytoplasm of type I pneumocytes, alteration of lamellar bodies and cristalysis of mitochondria of the type II pneumocytes.
It seems probable that the initial lesions of the lung in hemorrhagic shock are intravascular adhesion of leukocytes and perivascular edema. The rare occurrence of microthrombi is a striking feature of this cases in comparision to traumatic or septic shock.

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In 54 tunnel mining workers and 71 normal male subjects, we examined the levels of serum protease inhibitors such as α₁antitrypsin (α₁-AT), α₁antichymotrypsin (α₁-X), antithrombin III (ATIII), inter-α-trypsin inhibitor (IαTi), α₂macroglobulin (α₂-M) and Clsinhibitor (Cli) using micro single radial immunodiffusion methods.
1. The levels of α₁X were significantly (p<0.05) lower in workers than in normal male subjects, while levels of Cli were significantly (p<0.05) higher in such workers than in the normal control. The values of α₁AT, ATIII, IαTi and α₂M tended to be lower in workers than in normal subjects.
2. The values of IαTi, α₁X and Cli changed significantly (p<0.05) among three stages of pneumoconiosis (PR₂, PR₃, PR₄).
3. In tunnel mining workers the changes of Cli significantly (P<0.05) correlated with those of FEV 1.0% and the same trend was seen in the case of ATIII versus FEV 1.0% (P<0.1).
4. Regression analysis of the values of those protease inhibitors revealed a significantly positive correlation among protease inhibitors such as α₁-AT-α₂-M-ATIII, ATIII-α₂M-Cli, α₁X-IαTi and α₁X-Cli. Partial regression analysis of the values of ATIII showed a negative correlation tendency with years exposed to earth dust and the same trend was seen between α₁X and pack years smoked.
In our results and those reported in allied literature we discuss the important role of protease inhibitors in tunnel mining workers.

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As experimentally shown, pulmonary vasculature can be physiologically divided into extra-alveolar vessels and intra-alveolar vessels. The former are composed of pulmonary artery and vein running in the lung interstitium and the latter, capillaries exposed in alveolar space. They show entirely different geometrical responses to a change of lung volume, namely, an increase of cross-sectional area (a decrease of vascular resistance) in extra-alveolar vessels and an decrease (an increase of vascular resistance) in intra-alveolar vessels.
Arteriovenous fistula is a unique clinical condition to test the above-mentioned vascular physiology in man. This is because two vascular channels, a normal one composed of arterial, capillary and venous compartments and an abnormal composed of arterial and venous compartments lacking intra-alveolar vessels, run parallel in this pathological condition.
In this report, studies from this view point were carried out in 2 cases of pulmonary arteriovenous fistula. P_aO₂ under pure oxygen breathing changed, evidently due to a voluntary change of lung volume, the minimum in the TLC level and maximum in the RV level. Rather drastic, but identical P_aO₂ changes were observed during a passive change of lung volume under general anesthesia due to increases of airway pressure from atmospheric to 40 cmH₂O. QS/QT was inversely proportional to these changes of P_aO₂. These results fit clearly with the behavior of geometrical changes of intra-alveolar and extra-alveolar vascular comparments during lung volume change experimentally proposed in animals.
Evaluations of the disease were simaltaneously carried out using pulmonary angiography, pulmonary artery occlusion test during right heart catheterization, perfusion lung scan with ^99mTc MAA and echocardiogram with contrast media in these patients, but it is clear that dynamic analyses of P_aO₂ during these procedures have equivalent significance with these meticulous tests in diagnosis of pulmonary arteriovenous fistula.

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A 28-year-old housewife was admitted to Seirei Hamamatsu Hospital on July 21, 1980 because of nonproductive cough, exertional dyspnea, weakness of legs and numbness of distal parts of extremities. She had been complaining of cough and low-grade fever since July 10, and one week before admission, the loss of sensation and numbness occured in both hands and feet. Neurological examination on admission revealed so-called glove and stocking type of paresthesia, hypesthesia in right anterior femoral region and motor weakness of bilateral legs. Lumbar puncture on the third hospital day yielded clear and colorless cerebrospinal fluid under normal pressure, containing 2 lymphocytes per cubic millimeter, 15mg. protein per 100ml and 52mg. glucose per 100ml. Rales were heard in both lungs and the chest x-ray film showed diffuse macular patterns throughout the lungs. Arterial blood gas studies with breathing room air showed PO₂ of 72.0mmHg; PCO₂ of 30.6mmHg. Sputum and cerebrospinal fluid cultures for bacteria or fungi were negative, but the culture for Mycoplasma pneumoniae were technically impossible in our hospital. Serologic studies on admission showed a cold agglutinin titer of 1:256 dilutions and the Mycoplasma complement fixation titer of 1:2048. Complement fixation titers to other various virus showed no increase. 200mg of doxycycline hydrochloride was administered daily since the third hospital day. On the sixth hospital day, respiratory symptoms and paresthesia had disappeared and the diffuse macular infiltrate on the chest x-ray film showed nearly complete resolution. On the other hand, the hypesthesia spreaded to still more distal and posterior parts of right leg, and moved to the left leg, but disappeared within a month.

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