Kosei Yasumoto

Langerhans cells and prognosis in patients with gastric carcinoma

Infitration of Langerhans cells (LC) and macrophages into tumor tissues was investigated using immunohistochemical methods, anti‐S‐100 protein and anti‐lysozyme antibodies in 174 cases of gastric carcinoma. Varying population densities of S‐100‐positive LC were noted in tumor tissues; lysozyme‐positive macrophages, however, were found in almost equal quantities. LC were mainly interspersed among the tumor cells, whereas macrophages were present in the stroma and around the necrotic foci. Although the survival time of patients with Stage I, II or IV gastric carcinoma did not relate to the density of LC, survival time in Stage III patients correlated well with the density of LC. In patients with a marked infiltration of LC, survival time was longer than in cases of only a slight infiltration (P < 0.001). Therefore, LC in immunological defense mechanisms of the host against the tumor may be clinically effective in a certain phase of tumor development.

Human-human hybridomas secreting antibodies specific to human lung carcinoma

SummaryHuman Namalwa cells were screened in serum-free medium and in 6-thioguanine, then fused with human lymphocytes from lymph nodes of lung adenocarcinoma cancer patients. Extensive testing using 14 lung cancer cell lines, 11 other cancer cell lines and 4 normal fibroblast lines identified monoclonal antibodies produced by 4 hybridoma clones that reacted specifically with lung adenocarcinoma cells. These monoclonal antibodies also reacted with lung adenocarcinoma tissues and not normal tissues or erythrocytes of any blood type. These hybridoma clones grew and stably secreted the antibodies in serum-free medium as well as in serum-containing medium.

Arterial Hypoxemia in Patients With Hepatic Cirrhosis

Pulmonary function tests were studied in 105 patients with cirrhosis of the liver who had no clinical or radiographical evidence of cardiopulmonary disease. Spirometric data such as VC, FRC, RV, TLC, RV/TLC and FEV1.0% were within normal limits in all subjects. However, flow-volume curve and closing volume curve were abnormal in the majority. In flow-volume curve, &OV0312;25, was decreased and the &OV0312;50/&OV0312;25 value was increased; on the other hand, closing volume was markedly increased and FRC-CC value was reduced in the patients with hepatic cirrhosis. The closing capacity tended to exceed the FRC in the patients with arterial hypoxemia, indicating the presence of airway closure and gas trapping during resting ventilation. Therefore, ventilation-perfusion imbalance may be an important cause of arterial hypoxemia in patients with cirrhosis of the liver.

Mechanisms involved in acute lung edema induced in dogs by oleic acid

We investigated mechanisms related to the development of acute lung edema, as induced by oleic acid in adult mongrel dogs. The intravenous injection of oleic acid (0.04 ml/kg) was considered to induce a permeability edema, as an enhancement of transvascular protein clearance was observed after the injection. The effects of oleic acid injection on systemic blood pressure (SBP), pulmonary arterial pressure (PAP), pulmonary arterial wedge pressure (PAWP), cardiac output (CO) and airway pressure (AWP) were measured. A significant decrease in CO and increase in AWP were evident after the injection, but there were no changes in SBP, PAP and PAWP. Treatment of the animals with prostaglandin I2 (PGI2) did not alter the induction of edema by oleic acid. However, the decrease in CO and increase in AWP were normalized by treatment with PGI2. Blood platelet count was not affected by oleic acid given in a dose of 0.04 ml/kg. To determine the direct effect of oleic acid on the vascular endothelium, the agent was injected through a catheter placed in the pulmonary artery. Electron microscopic examination revealed severe vacuolation on the endothelium of the pulmonary artery after only 1 min of exposure to oleic acid. Increased permeation of Evans blue into the subendothelial tissue was also observed with oleic acid treatment, compared with findings in the controls. These results indicate that the lung edema induced by oleic acid is due to an increased protein clearance, probably through a direct toxic effect on the vascular endothelium rather than an indirect toxic effect of chemical mediators released from the aggregated platelets.

Results of Surgical Treatment of Patients with T3 Non—Small Cell Lung Cancer

Sixty-one patients with T3 non-small cell lung cancer were surgically treated in our department from February, 1974, through April, 1986. The overall 5-year survival, excluding patients with pleurisy, was 23%, and the 5-year survival for patients undergoing complete resection and incomplete resection was 42% and 10%, respectively (p less than 0.01). Survival in patients with T3 N0 and T3 N1 or N2 disease was 33% and 0 at 5 years, respectively. The prognosis for patients with pleurisy was poor, and all died within 3 years. Therefore, complete lung resection should be done in patients with T3 N0 non-small cell lung cancer if complete resection is expected. Long-term survival is less likely for patients with lymph node metastases if complete resection cannot be performed.

Generation and expansion of lymphokine-activated killer cells from lymph node lymphocytes in human lung cancer

We cultured lymph node lymphocytes (LNL) from lung cancer patients in the presence of recombinant interleukin 2 (rIL2). The ability of LNL to respond to rIL2 was not affected by the advance of cancer stage when tested for proliferation and for lymphokine-activated killer (LAK) activity. The LAK activity of LNL was comparable to that of the corresponding peripheral blood lymphocytes. The rIL2-induced proliferation of macrophage-depleted LNL was augmented by the reconstitution with autologous alveolar macrophages while the LAK activity was not affected. However, macrophage-reconstituted LNL expanded rapidly and reached higher cell densities and exhibited a significantly lower LAK activity than macrophage-depleted LNL. The diminished LAK activity in macrophage-reconstituted LNL were markedly augmented by the subculture at a low cell density. From these results, we conclude that LNL can be a good material for the postoperative LAK therapy and that macrophage is useful in culture of LAK cells.

Histone H2B as an antigen recognized by lung cancer–specific human monoclonal antibody HB4C5

Histone H2B was demonstrated to be an immunoreactive material recognized by the human monoclonal antibody HB4C5, which had been already established to be specific for lung cancers. The inhibitory effect of histone H2B on the activity of HB4C5 antibody to immunostain the cytoplasmic antigen in lung adenocarcinoma tissue indicated that histone H2B at least had antigenic determinant comparable to the cytoplasmic antigen. A mouse anti-histone H2B monoclonal antibody could immunostain the cytoplasm of lung adenocarcinoma cells in sliced tissue sections in the same manner as the human monoclonal antibody HB4C5. Enzyme-linked immunosorbent assay of HB4C5 antibody on plastic immunoplates coated with histone H2B also showed specific reactivity of this antibody with histone H2B, and the reaction was effectively inhibited when extra histone H2B or mouse anti-histone H2B monoclonal antibody was added to the reaction mixture. These results consistently lead us to a conclusion that histone H2B possesses antigenicity to the human monoclonal antibody HB4C5.

Endotracheal Neurilemoma with a Lymphoid Cuff. An Ultra structural and Immunohistochemical Study

A neurilemoma occurred in the trachea of a 63 year old woman complaining of dyspnea. Microscopically, the excised tumor was composed prodominantly of cellular areas of Antoni type A tissue and had a peripheral lymphoid cuff. The schwannian origin was confirmed both immuno‐histochemically and ultrastructurally. This tumor without nuclear palisading and Verocay bodies differed somewhat from a conventional soft tissue neurilemoma and closely resembled a particular form of neurilemoma of the stomach, previously reported as a unique entity. Thus, this type of neurilemoma does occur in sites other than the gastrointestinal tract. Acta Pathol Jpn 39:407 412, 1989.

Pulmonary Interstitial Edema in Experimental Cirrhosis of the Liver in Rats

To determine whether interstitial pulmonary edema occurs or not in experimental cirrhotic rats, male Sprague-Dawley rats were given carbon tetrachloride subcutaneously in order to induce liver cirrhosis. The percent lung water content of the cirrhotic rats increased to 79.1 +/- 0.7% compared to 77.4 +/- 0.9% in control rats (p less than 0.001). Microscopically, 8 of 10 cirrhotic rats show the pulmonary interstitial thickening with lymphocytic infiltration. Moreover, perivascular edema with dilatation of lymphatics was frequently recognized. This suggested that fluid retention of pulmonary interstitial tissue would occur in the cirrhotic rats, and then perivascular edema would compress the small airways of the lung in cirrhotic rats.

Serodiagnosis of cancer by using Candida cytochrome c recognized by human monoclonal antibody HB4C5

Cytochrome c from various sources, such as Candida krusei, yeast, horse, and cattle, was found to be recognized by human monoclonal antibody HB4C5 specific to lung cancer. Therefore, the cytochrome c was applied to the measurement of antibody amount in patient sera with a similar reactivity to the antibody HB4C5 for serodiagnosis of cancer. The cytochrome c from Candida krusei was most valuable for the serodiagnosis of various cancers, and the yeast cytochrome c was also useful. However, horse and bovine cytochrome c did not react with antibody of the cancer patients. By using Candida cytochrome c lung, bile duct, esophagus, and liver cancers were detected at high rates of more than 50%. In the case of lung cancer, the detection rates of small-cell, squamous, large-cell and adenocarcinoma were 78%, 63%, 100%, and 34%, respectively. The rate for small-cell carcinoma was higher than that with the currently used NSE assay system, and the rate for squamous carcinoma was comparable to that with the SCC assay system, although the system using cytochrome c did not show similar reactivity to that with the SCC system. Furthermore, lung cancer was detected at early stages by using cytochrome c, and even in the case of adenocarcinoma, the rate at early stages with the cytochrome c system was higher than that with the CEA assay system. On the other hand, false positive rates of benign diseases and normal were low--8% and 2%, respectively.