The relationship between platelet, prostaglandins and metastasis of cancer was investigated in 68 cases of primary lung cancer (26 cases with and 42 with out metastasis), 27 cases of benign lung disease, 14 cases of cerebral infarction and 42 helthy controls. The amount of Lipid peroxides in platelet, Thromboxane B₂, 6-keto-prostaglandin F_1α and the rate of Thromboxane B₂/6-keto-prostaglandin F_1α were measured. Three principal results were obtained. First, in the group having primary lung cancer with metastasis, the levels of lipid peroxides in platelet, Thromboxane B₂ and 6-keto prostaglandin F_1α in the serum, as well as the rate of Thromboxane B₂/6-keto prostaglandin F_1α were increased compared to the groups having lung carcinoma without metastasis, benign lung disease and the healthy controls. In addition, the positive rate of lipid peroxides in platelet and Thromboxane B₂ were also increased in this group as compared with the benign lung desease and healthy control groups. (Positive rate of lipid peroxides in platelats and Thromboxane B₂ was 73.1% and 42.3%). Second, the amount of lipid peroxides in platelet showed a positive correlation compared with Thromboxane B₂ (p<0.01, r=0.414), the lipid peroxides in platelet method was considered to be a useful marker as Thromboxane A₂ activity was the same as Thromboxane B₂. The method was also concluded to be useful clinically, because it enabled only a small sample to be examined. Third, maximum platelet aggregation rate of ADP (1×10^-6M, 1×10^-5M), collagen, epinephrine demonstrated no correlation compared with the amount of lipid peroxides in platelet or Thromboxane B₂/6-keto prostaglandin F_1α.

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From the viewpoint of auscultation, it is reasonable to try to establish classification indices of crackles through spectrum analysis. We studied the power spectrum of a crackle by the linear predictive coding (LPC) method. With this method, it was possible to study a spectrum as a set of numerals and evaluate the crackle objectively. We studied 28 crackles (15 cases) in various diseases and obtained 28 spectrum envelopes (LPC cepstrums). When the crackle had been defined by the length of its first peak to the second peak of wave form (=CD/2, coarse crackle>1.1 msec., fine crackle≤1.1 msec.), they correlated well with the result of auscultation (12/15 cases, 87%). The first cycle of a crackle determined almost all of the power spectrum. This result suggested that it was reasonable to classify the fist part of the wave form.
We could classify 28 cepsutrums into 2 main and 5 sub-groups based on their figures. Two sub-groups were defined as coarse and three sub-groups were defined as fine by the CD/2 definitions. From the viewpoint of power spectra, we could define coarse crackes as those in which the peak frequency was 150-250Hz and the maximum frequency (frequency at the sound pressure decreased by 20dB from the level of the maximum pressure frequency) was 700-750Hz and those of fine crackles were 350-400 and 1.5Hz respectively.
We compared the availability of some LPC parameters with those of CD/2. The maximum pressure frequency (Fmax.) and K parameter correlated significantly with CD/2 (p≤0.01). The K1 separated the crackles better than Fmax. The K parameters are pure correlations between two data points and reflect the power spectrum. We concluded that the K1 parameter was a unique and useful spectrum index.

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Chronic diffuse lung diseases such as idiopathic interstitial pneumonia (IIP), sarcoidosis and pneumoconiosis manifest inflammation, injury and fibrosis in pulmonary interstitium with debilitating and fatal consequences.
Lung collagen and Fibronectin (FN) in these diseases may play major roles in the interstitial tissue fibrotic process.
We attempted to measure type III procollagen peptide (PIIIP) in the sera and bronchoalveolar lavage fluids (BALF) and to measured FN in the BALF in 110 patients with various pulmonary diseases.
Serum levels of PIIIP in IIP, lung tuberculosis and pneumoconiosis were higher than those of normal controls. BALF levels of PIIIP in sarcoidosis, IIP and pneumoconiosis were higher than those of other lung diseases or normal controls. BALF levels of FN in sarcoidosis and IIP were higher than those of normal controls. BALF levels of PIIIP and FN were more elevated in the acute type of IIP and the acute phase of sarcoidosis than in the chionie type of IIP or the inactive phase of sarcoidosis respectively.
These data suggested that both synthesis of PIIIP and FN were increased in the active phase rather than the phase of fibrotic manifestation of these diseases. The values of PIIIP and FN may be useful markers of disease activity, but they do not directly represent the fibrotic process.

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To evaluate the clinical usefulness of X-ray CT for diagnosis of emphysema, we studied CT findings of lung in patients with chronic obstructive ventilatory impairment and compared them with the results of lung function tests and selective alveolobronchography (SAB).
To clarify the clinical significance of CT findings, the correlation between parameters of evaluation by CT and lung function data were studied in 42 patients. Mean CT numbers of lung fields and low attenuation area (CT No. <-950. H. U.)% were well correlated with lung volumes and DL_CO/V_A. Particularly the correlation between the low attenuation area % and DL_CO/V was high. Differences of the CT number in the lung field correlated well with %RV and RV/TLC%. Although low attenuation area % was considered to be the most appropriate parameter among the three for diagnosis of emphysema, the effect of lung volume on this parameter could not be ruled out.
In thirty-one patients SAB was performed along with CT and lung function tests. CT findings were evaluated by low attenuation area % and visual score. To establish a visual scoring system for diagnosis of emphysema, CT imagings were classified into Type I and Type II as follows; Type I was characterized by scattered small low attenuation areas like worm-eaten holes. Type II was characterized by broad and uneven low attenuation areas. Using six lung slices for each patient, we scored CT findings based on this classification as follows; No signs of emphysema: 0, possible signs of emphysema: 0.5, slight but definite signs of emphysema: 1, marked signs of emphysema: 2. The sum of these scores (minimum: 0-maximum: 12) was used for diagnosis. The CT visual score is a very sensitive and specific parameter for diagnosis of emphysema, because the CT visual score was 5 or above in patients whose SAB images suggested emphysema and 2 or below in patients whose SAB images did not suggest emphysema. The differences of CT visual scoring among four chest physicians were relatively small. Furthermore the CT visual scoring system was far more accurate for diagnosis of emphysema than lung function tests. On the other hand low attenuation area % did not allow discriminantion between patients with emphysema and without emphysema.
Based on these results, we concluded that our CT scoring system is a noninvasive and very useful method for diagnosis of emphysema in patients with chronic airway obstruction.

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Airway responsiveness to methacholine, histamine, prostaglandin F_2α (PGF_2α) and leukotriene D₄ (LTD₄) was studied in 12 patients with aspirin-induced asthma (AIA), 13 patients with extrinsic asthma and 12 patients with intrinsic asthma. An aerosol of each agent was inhaled in two-fold increasing concentrations. The FEV₁ was measured before and immediately after each inhalation to check the airway response. Inhalation was discontinued when the FEV₁ fall 20% or more below the baseline value, and further measurement of FEV₁ was made every 10min until 60min after the last inhalation to check the time course of the effect of each agent. The provocation concentration of agent producing a 20% fall in FEV₁ (PC₂₀) was determined from the log dose-response curve by linear interpolaton between the last two points. The slope (ΔFEV₁) was calculated by linear interpolation between the two points, 12% and 20% decrease in FEV₁ on the log dose-response curve.
There were no significant differences in PC₂₀ and ΔFEV₁ in all of the agents. However, delayed recoveries in FEV₁ after challenge with PGF_2α and LTD₄ were observed in the AIA group, but not in the other groups. These results suggest that in AIA there might be some defects in the regulatory mechanism concerning relaxation of bronchial muscles, especially in the local formation of bronchodilator prostaglandins such as PGE₂ or PGI₂, or in the degradation pathway of the arachidonic acid metabolites such as PGF_2α or LTD₄.

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In order to clarify the mechanisms of injury of the alveolar structure and fibrotic process in diffuse interstitial lung deseases and to examine the usefulness of bronchoalveolar lavage fluid (BALF) as a material for investigating the pathogenesis of interstitial lung diseases, we examined the effect of BALF from bleomycin-treated rats on in vitro fibroblast proliferation.
Bleomycin (0.9mg) was once administered to male Wistar strain rats weighing about 200g via trachea, and bronchoalveolar lavage was carried out at 2, 3, 6, 15 and 29 days after administration. The BALF was centrifuged at 250×g for 10min to remove cells, and thereafter centrifuged at 27, 000×g for 40min to remove pulmonary surfactant. The resultant supernatant was concentrated 10-fold by ultrafiltration. The effects of the concentrated BALF on fibroblast growth was tested in vitro; fibroblasts (IMR90) in Go stage were cultured in Dulbecco's modified Eagle medium with BALF or control saline, and their numbers were determined by the method of Zacharchuk et al., in which the absorbance at 550nm of solubilized fibroblasts was measured after crystal violet stain of only viable fibroblasts.
At 2 days after administration, no fibroblast growth factor activity was detectable but cytotoxic factor activity was detectable in the BALF. At the same time, a change corresponding to the initial stage of diffuse interstitial pneumonia was observed in the lungs on histological examination, and moreover prominent increases of the numbers of neutrophils and eosinophils were found on analysis of cells in the BALF. It is postulated that the cytotoxic factor may be related to injury of the alveolar structure, and at least a part of the cytotoxic factor may be released from neutrophils and eosinophils.
On the other hand, at 3 days after administration, the cytotoxic factor activity was not detectable, and increase of growth factor activity for fibroblasts over that of control rats was found in the BALF from the bleomycin-treated rats. The level of the growth factor activity was slightly lower at 6 days than at 3 days after the administraiton and was equal to that of control rats at 15 and 29 days after the administration. On histological examination, fibroblast proliferation in the alveolar walls was most marked at 6 days, gradually decreasing thereafter, and interstitial pulmonary fibrosis was observed at 15 days after administration, . From these results, it is considered that the growth factor detected in the BALF at 3 and 6 days after administration may be closely related to the fibroblast growth and the development of pulmonary fibrosis in the blemycin-induced interstitial pneumonia-fibrosis.
These results suggest that analysis of BALF is useful to investigate the mechanisms of interstitial pneumonia and subsequent pulmonary fibrosis.

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Alveolar macrophages (AM) might regulate fibroblast proliferation in the development of pulmonary fibrosis. However, results were not identical. Namely, some investigators reported that AM stimulated the lung fibroblast growth, but the others pointed to AM inhibition. In searching these conflicting results, it is important to compare the experimental results in the same conditions. There is a tendency that investigators supporting AM inhibition do the fibroblast proliferation assay under a 10% fetal calf serum (FCS) condition, and researchers describing the AM stimulation avoid the assays under a 10% FCS by using a platelet free plasma (PFP) or a low FCS concentration (0.4%). In this report, we recovered AM from normal rats and hamsters instilled with or without bleomycin, and prepared silica-stimulated AM culture supernatnats. These supernatants stimulated the lung fibroblast growth under a 5% PFP condition, and inhibited it under a 10% FCS condition. One of the reasons about these conflicting results may be ascribed to the difference in the fibroblast culture conditions. However, the inhibition observed under a 10% FCS condtion was considered to be a fibroblast “self regulation” for a “growth factor excess condition” that was caused by the addition of AM-derived growth factors (interleukin-1 or macrophage-derived growth factor (MDGF)) to a 10% FCS medium, rather than to be an AM-derived inhibition. Because; 1) the fibroblast showed the maximum growth under a 10% FCS condition, and over that concentration the fibroblast growth was inhibited, and 2) under a 10% FCS condition, even a well-known growth factor, platelet-derived growth factor (PDGF) inhibited the fibroblast proliferation without an FCS and enhance pulmonary fibrosis. It was suggested that the inhibition of the activation might be important in the therapy of pulmonary fibrosis.

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Two monoclonal antibodies, AMH-2 and AMH-3, raised against human lung macrophages in bronchoalveolar lavage fluid, alveolar spaces and interstitia of lung tissue are described. The antibodies were produced by immunizing mice with bronchoalveolar lavage cells. Both monoclonal antibodies reacted with macrophages in bronchoalvelar lavage fluid and alveolar spaces, but they showed different reactivity patterns with monocytemacrophage lineage. Although AMH-2 reacted wealky with blood monocytes and with some interstitial macrophages, it did not react with peritoneal macrophages. AMH-3 did not react with either blood monocytes or peritoneal macrophages, but was positive for most interstitial macrophages. There was a correlation between the reactivity patterns of both antibodies to macrophages in bronchoalveolar lavage fluid and patients' smoking habits. Most significantly, epithelioid cells of lung granulomas obtained from patients with sarcoidosis and hypersensitivity pneumonitis were strongly stained by both AMH-2 and AMH-3. Differences between the two antibodies in their reactivities with macrophages and granulomas in lungs indicate that lung macrophages contain heterogenous populations that are in various states of differentiation and maturation, and that the epithelioid cells and lung macrophages share the same membrane antigens. Therefore, these antibodies may be useful for investigating subpopulations and functions of macrophages in lungs and for clarifying the pathogenesis of granulomatous lung diseases.

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A monoclonal antibody 6F9 (IgG1) was obtained through fusion between mouse myeloma cells (SP2/0) and spleen cells of mice (BALB/c) immunized with a human lung cancer cell line NULC2 (poorly differentiated adenocarcinoma).
The serological specificity of 6F9 was analyzed by an anti-mouse Ig hemadsorption (MHA) test on a panel of human cell lines and an immunohistochemical method using frozen sections. Although 6F9 showed a broad spectrum without any specificity in the MHA tests, the immunohistochemical reactivity of 6F9 was restricted to squamous cellular tissues. Treatments by heat or enzymes of the antigen recognized by 6F9 suggested that the antigenic determinant was a carbohydrate chain of a glycoprotein without terminal sialic acid.
To establish differential diagnosis of lung cancers, immunohistochemical methods of stamp cytological specimens were examinaed. Four out of 6 squamous cell carcinomas of the lung showed positive staining, and neither six adenocarcinomas nor two large cell carcinomas proved negative.
6F9, therefore, may be a useful reagent for cytological differential diagnosis of lung cancers.

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To evaluate the effect of smoking on dynamics of amine in the lung, we developed the I-123IMP lung dynamic scanning method. Age-matched 5 non-smokers, 5 ex-smokers and 5 smokers were examined with the I-123 IMP dynamic scintigraphy. The individual intravenous bolus dosages were 3mCi and data were recorded in 360-sec frames (1 frame/1.5sec) using the GE 400 AC/T, a low-energy general purpose collimetor. Regions of interest (ROIs) were assigned for the right and left middle lung fields and the heart. The time-activity curves were generated from these ROIs, and the exponential curve-fitting was performed and the time constant (Tc) was calculated using the statistic analysis system.
Count=A×EXP (Time/Tc)+C
The time constant was significantly higher in the group of smokers (67.71±2.15) than in both group of non-smokers (46.88±4.10) and group of ex-smokers (49.28±4.82) (p<0.002). The washout of I-123 IMP from the lung was delayed in the group of smokers.
Our results indicate that smoking influenced the early dynamics of I-123IMP in the lung, and that such non-invasive analysis in the early phase may prove useful for the human study of amine metabolism in the lung.

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In order to establish suitable assay methods for fucose and sialic acid contents in sputum and serum, and to examine their diagnostic values in sputum and serum of patients with lung diseases, assays were performed by method I, a colorimetric method without isolation of these sugars and by method II involving isolation of these sugars using HPLC.
In method I, the fucose content was measured by the method of Gibbons, a colorimetric method without isolation from other sugars. In method II, the fucose content was measured by a colorimetric method using 2-cyanoacetamide method after it was isolated from other sugars by HPLC using Aminex HPX-87. It was shown that fucose concentration measured by method I was about 3-fold higher in serum and 1.4- fold higher in purulent sputum than the value obtained by method II, while it was almost the same as the latter in mucoid sputum. This result indicates that method I is not suitable for assay for fucose content in serum or purulent sputum although it yields accurate measurement of fucose content in mucoid sputum.
The sialic acid concentration value obtained by measurement with method I, the TBA method was almost the same as that by method II, in which the concentration was estimated by absorbance at 200nm after isolation by HPLC, not only in mucoid sputum but also in serum and purulent sputum, indicating that the sialic acid concentration in these samples can be accurately measured by the TBA method, a conventional colorimetric method.
It was shown by gel filtration and DEAE-Sephacel column chromatography that considerable amount fucose and sialic acid in serum are distributed to different proteins of glycoproteins from each other, and about 35% is distributed to IgG in serum of normal subjects. It was also shown that changes in serum fucose concentration are caused by those in the concentrations of both IgG and components other than IgG. It was suggested that the serum fucose level has a diagnostic value different from that of serum N-acetylneuraminic acid (NANA) level in patients with lung diseases.
It was confirmed by method II that NANA content of purulent sputum is higher than that of mucoid sputum while there is no significant difference between the fucose content of mucoid and purulent sputum in patients with chronic airway diseases.

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A case of pulmonary plasma cell granuloma is reported. A 53-year old man was admitted with complaints of fever and chills. Chest X-ray examination revealed two abnormal tumor-like lesions, one in the left middle lung field and the other in the right lung. Antibiotics were administered for three months and the right lung field lesion disappeared completely. However, the abnormal shadow in the left chest increased in size. Therefore the left lung lesion was diagnosed as lung cancer, and left partial lobectomy we performed. the dissected specimen included a round, elastic hard nodular lesion, the cut surface of which was yellowish-white in color. The histologic study of the nodule revealed severe infiltration of plasma cells associated with macrophages, neutrophiles, fibroblasts and capillally proliferation. The plasma cells showed well-matured features cellular atypism nor mitoses. Immunohistochemical examination for the plasma cells using anti-IgG, IgM and IgA-antibody showed a polyclonal nature, and a diagnosis of plasma cell granuloma was established. These histologic fundy and the fact that the patient had a preceding infectious lesion which was showed by the chest X-ray exaination strongly suggest inflammatory origin.

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A case of Waldenstrom's macrogloblinemia (WMG) with principally pulmonary manifestation was reported. The patient was a 58 year-old man in whom an abnormal chest shadow in the right lower lung field was noted on chest X-ray examination in 1979. He was admitted to our hospital in June 1983, because the abnormal shadow had increased. His total serum protein was 8.2g/dl.
M-protein of the IgM lambda type was observed on serum immunoelectrophoresis. Superficial lymph nodes and the spleen were not enlarged. No abnormal peripheal blood findings were seen.
An open lung biopsy was performed, because a WMG lung lesion was suspected due to the transbronchial biopsy fundings. The right lobe was as hard as the liver. Histologic examination showed dense monotonous lymphoplasmacytoid infiltration. Studies by the PAP method revealed monoclonal cytoplasmic immunogloblin of the IgM lambda type.

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A case of primary pulmonary cryptococcosis is presented. A 20-year-old woman complainning of fever and exertional dyspnea was admitted. Chest X-ray revealed diffuse infiltrative shadows throughout both lower lung fields and small nodular shadows in the upper lung fields. Diagnosis of pulmonary cryptococcosis was made by transbronchial lung biopsy and bronchial washing. Delayed type hypersensitivity proved by skin test was attenuated in challenges by PPD and PHA.
The majority of primary pulmonary cryptococcosis cases show a solitary nodule or infiltration limited to a single pulmonary lobe. The reason for the wide-spread distribution of the lesions in this case might be due to poor cell immunity, resulting in infection by Cryptococcus neoformans.

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