Evidence of acute inflammatory response in reexpansion pulmonary edema.

We analyzed edema fluid in two cases of reexpansion pulmonary edema during thoracotomy. High value of the fluid to plasma protein concentration ratio indicates an increase in pulmonary microvascular permeability. There were marked increases in polymorphonuclear leukocyte (PMN) count and concentration of PMN-elastase in edema fluid. There were also increases in concentrations of thromboxane B2 and 6-keto-PGF1-alpha in both edema fluid and plasma. These findings strongly suggest that the mechanism of reexpansion pulmonary edema is an inflammatory response and that PMNs in the reexpanded lung may play a role in the increase in permeability.     

Anatomy,histology and elemental profile of long bones and ribs of the Asian elephant (<Emphasis Type="Italic">Elephas maximus</Emphasis>)

This study evaluated the morphology and elemental composition of Asian elephant (Elephas maximus) bones (humerus, radius, ulna, femur, tibia, fibula and rib). Computerized tomography was used to image the intraosseous structure, compact bones were processed using histological techniques, and elemental profiling of compact bone was conducted using X-ray fluorescence. There was no clear evidence of an open marrow cavity in any of the bones; rather, dense trabecular bone was found in the bone interior. Compact bone contained double osteons in the radius, tibia and fibula. The osteon structure was comparatively large and similar in all bones, although the lacuna area was greater (P < 0.05) in the femur and ulna. Another finding was that nutrient foramina were clearly present in the humerus, ulna, femur, tibia and rib. Twenty elements were identified in elephant compact bone. Of these, ten differed significantly across the seven bones: Ca, Ti, V, Mn, Fe, Zr, Ag, Cd, Sn and Sb. Of particular interest was the finding of a significantly larger proportion of Fe in the humerus, radius, fibula and ribs, all bones without an open medullary cavity, which is traditionally associated with bone marrow for blood cell production. In conclusion, elephant bones present special characteristics, some of which may be important to hematopoiesis and bone strength for supporting a heavy body weight.     

Lung function after lobectomy in chronic pulmonary emphysema

We compared the prediction of postoperative pulmonary function in two groups: chronic pulmonary emphysema (CPE) group (n = 30) and normal control group (n = 41). These patients had a lobectomy because of lung cancer. We measured pulmonary function test (FVC, EFV1, TLC, FRC, RV, DLco), and pulmonary perfusion scan before and after surgery. We found correlation between the predicted and measured postoperative values very close in control group. Whereas, in CPE group, these correlations were very low especially in FVC and FEV1. We also calculated the pulmonary function on the operated and the non-operated sides. The correlation were very high without FEV1 in control group and all the measured values did not correlate to the predicted values. On the non-operated side, the correlations were high in both control and CPE groups. From these results we can conclude that it is difficult to predict the postoperative pulmonary function in the case of chronic pulmonary emphysema.     

Correlated Expression of Glutathione S-Transferase-π and c-Jun or Other Oncogene Products in Human Squamous Cell Carcinomas of the Head and Neck: Relevance to Relapse after Radiation Therapy

The expression of glutathione S -transferase (GST)-π and four oncogene products, c-Jun, c-Fos, c-H-Ras, and c-Myc, in human squamons cell carcinomas of the head and neck was investigated immunohistochemically before and after radiation therapy, to examine whether these oncogene products might be involved in GST-π expression, and also to examine the relationship between their expression and therapeutic response. Clinical response to radiation was evaluated in terms of both tumor regression and relapse over two-year follow-up periods. The overall positive rates in 83 carcinoma specimens before therapy were 60.2% for GST-π and 28.9–51.8% for the individual oncogene products, the positive rates for the oncogene products being higher in GST-π-positive than in GST-π-negative cancers. c-Jun was most highly correlated with GST-π expression. Following radiation, the expression of GST-π and the oncogene products was altered in about a half of 30 patients. Eleven of the 18 patients who exhibited prior positivity for GST-π showed negative conversion, while 4 of the 12 patients with prior negativity demonstrated positive conversion. In most cases, changes in c-Jun staining coincided with those in GST-π. Regarding clinical response to radiation therapy, the positive rates for GST-π and c-Jun before radiation were higher in the residual cancer or relapse cases than in the group showing complete response without relapse. Examination of 26 patients with laryngeal cancer revealed that relapse occurred more frequently in cases exhibiting positive reactions for GST-π,c-Jun, or c-H-Ras. These results suggest a direct link between c-Jun and GST-π in head and neck cancers before and after radiation. Although GST-π and the oncogene products can be influenced by radiation, GST-π and c-H-Ras expression may be a risk factor for relapse of laryngeal cancer.     

Successful treatment of mogamulizumab‐resistant mycosis fungoides with mogamulizumab plus etoposide combined therapy: Investigation of the immunomodulatory effects of etoposide on the tumor microenvironment

Mogamulizumab shows cytotoxicity against CCR4+ lymphoma cells by antibody‐dependent cell‐mediated cytotoxicity (ADCC) in advanced cutaneous T‐cell lymphoma (CTCL) patients. Although mogamulizumab is used as one of the anchor drugs for the treatment of advanced CTCL, its efficacy is unsatisfactory, especially in mycosis fungoides (MF). Therefore, additional drugs to enhance the antitumor effects of mogamulizumab are needed to further optimize its use for the treatment of MF. In this report, two cases of mogamulizumab‐resistant MF successfully treated with additional administration of etoposide are presented. Moreover, the possible mechanisms of mogamulizumab‐etoposide combined therapy for the treatment of MF were investigated based on the modulation of chemokine profiles in vivo using an EL‐4 mouse T‐cell lymphoma model. Intraperitoneal administration of etoposide significantly increased the mRNA expressions of CCL17, CXCL5, and CXCL10, suggesting that CCR4+ CTCL cells gather around the tumor‐associated macrophagess. Furthermore, the immunomodulatory effects of etoposide on the mRNA expressions of these chemokines were validated using monocyte‐derived M2 macrophages in vitro. Since mogamulizumab shows cytotoxicity against CCR4+ lymphoma cells by ADCC that depends on the contact between the lymphoma cells and the effector cells, these chemokines could enhance the therapeutic effect of mogamulizumab.     

Immunoelectron microscopic examination of IgA deposition in dermatitis herpetiformis

Ultrastructural localization of IgA in the skin of three Japanese patients with dermatitis herpetiformis (DH) was studied with the immunoelectron microscopic technique using periodate-lysine-paraformaldehyde fixation. In direct immunofluorescence studies, two of the three cases showed fine fibrillar deposition of IgA and the other case fine granules in the dermal papillae. In the former, the reaction products of IgA were present in the upper dermis forming various-sized aggregates which were occasionally arranged perpendicularly to the epidermis and appeared to be associated with microfibrillar bundles of the elastic tissue. Reaction products were also deposited to a lesser extent on the microfibrillar component of the elastic fibers at the lower part of the dermal papillae. However, in the latter, the reaction products were found to form smaller aggregates on and around the collagen fibrils rather than on the elastic tissue. Such a localization of IgA reaction products has not yet been reported in DH. The difference of the distribution patterns of IgA and the possible singularity of Japanese DH cases are discussed.     

Evaluation of cardio-pulmonary function for lobectomy under the condition of selective pulmonary arterial occlusion test (SPAO)

We performed selective pulmonary arterial occlusion test (SPAO) and unilateral pulmonary arterial occlusion test (UPAO) in 30 patients with lung cancer who would be undertaken right lower lobectomy or middle and lower lobectomy, and evaluated the preoperative cardio-pulmonary function. The lung hemodynamics during SPAO were different from those during UPAO. This indicates that SPAO evaluated reserve capacity of vascular bed in the right upper lobe which would be remained at the surgery. Moreover, the ratio of total pulmonary vascular resistance during SPAO to that of before SPAO was not differed in two groups, one was a group with and the other was a group without impaired reserve capacity of vascular bed in the contralateral lung. This suggests that reserve capacity of pulmonary vascular bed including right upper lobe would be well compensated even in the patients with highly impaired capacity in the contralateral lung. Based on these findings, we performed lung resections in 9 patients, who were judged contraindications for lung resection by the results of UPAO, and no patient suffered postoperative cardio-pulmonary complications. Total pulmonary vascular resistance immediately after the right middle and lower lobectomy were equal to those during SPAO. Thus we conclude that SPAO is very useful technique for evaluating cardiopulmonary function after right lower lobectomy or middle and lower lobectomy, and that it would be possible to extend the boundaries of safety for lung resection based on evaluation of cardio-pulmonary function by SPAO.     

Assessment of systematic nodal dissection by VATS lobectomy for lung cancer

The feasibility of the complete systematic nodal dissection by the video-assisted thoracic surgery was prospectively assessed in 22 cases of clinical stage I lung cancer (16 right, 6 left cases). Resection of the designated lobe with the mediastinal lymph node dissection was carried out by the small thoracotomy with the aid of the thoracoscope, followed by the standard surgery to verify the completeness of systematic nodal dissection. Although residual lymph nodes were found in 14 of 22 cases, the residual rate was 2.9% and 2.7% by the number and 2.3% and 2.1% by the weight in right and left cases, respectively. Average time and hemorrhage for performing the procedure were 196 minutes, 216.7 minutes and 157.5 g, 145 g in right and left cases, respectively. As a consequence, sufficient systematic nodal dissection in lung cancer was suggested to be feasible by VATS lobectomy.