Enhanced Autophagy and Reduced Expression of Cathepsin D Are Related to Autophagic Cell Death in Epstein-Barr Virus-Associated Nasal Natural Killer/T-Cell Lymphomas: An Immunohistochemical Analysis of Beclin-1, LC3, Mitochondria (AE-1), and Cathepsin D in Nasopharyngeal Lymphomas

This study investigated autophagy in 37 cases of nasopharyngeal lymphomas including 23 nasal natural killer (NK)/T-cell lymphomas (NKTCL), 3 cytotoxic T-cell lymphomas (cytotoxic-TML) and 9 B-cell lymphomas (BML) by means of antigen-retrieval immunohistochemistry of beclin-1, LC3, mitochondria (AE-1) and cathepsin D. Peculiar necrosis was noted in EBV+ lymphomas comprising 21 NKTCL, 2 cytotoxic-TML and 1 BML. Lymphomas without peculiar necrosis showed high expression of beclin-1, macrogranular cytoplasmal stain of LC3 with sporadic nuclear stain, a hallmark of autophagic cell death (ACD), some aggregated mitochondria and high expression of cathepsin D, suggesting a state of growth with enhanced autophagy with sporadic ACD. EBV+ NKTCL with the peculiar necrosis, showed significantly low level of macrogranular staining of LC3, aggregated mitochondria and low expression of cathepsin D in the cellular areas when degenerative lymphoma cells showed decreased beclin-1, significantly advanced LC3-labeled autophagy, residual aggregated mitochondria and significantly reduced expression of cathepsin D, suggesting advanced autophagy with regional ACD. Consequently it was suggested that enhanced autophagy and reduced expression of lysosomal enzymes induced regional ACD under EBV infection in NKTCL

Development of Ultra-Super Sensitive Immunohistochemistry and Its Application to the Etiological Study of Adult T-Cell Leukemia/Lymphoma

Antigen retrieval (AR) and ultra-super sensitive immunohistochemistry (ultra-IHC) have been established for application to archival human pathology specimens. The original ultra-IHC was the ImmunoMax method or the catalyzed signal amplification system (ImmunoMax/CSA method), comprising the streptavidin-biotin complex (sABC) method and catalyzed reporter deposition (CARD) reaction with visualization of its deposition. By introducing procedures to diminish non-specific staining in the original ultra-IHC method, we developed the modified ImmunoMax/CSA method with AR heating sections in an AR solution (heating-AR). The heating-AR and modified ImmunoMax/CSA method visualized expression of the predominantly simple present form of HTLV-1 proviral DNA pX region p40Tax protein (Tax) in adult T-cell leukemia/lymphoma (ATLL) cells in archival pathology specimens in approximately 75% of cases. The simple present form of Tax detected exhibited a close relation with ATLL cell proliferation. We also established a new simplified CSA (nsCSA) system by replacing the sABC method with the secondary antibody- and horse radish peroxidase-labeled polymer reagent method, introducing the pretreatments blocking non-specific binding of secondary antibody reagent, and diminishing the diffusion of deposition in the CARD reaction. Combined with AR treating sections with proteinase K solution (enzymatic-AR), the nsCSA system visualized granular immunostaining of the complex present form of Tax in a small number of ATLL cells in most cases, presenting the possibility of etiological pathological diagnosis of ATLL and suggesting that the complex present form of Tax-positive ATLL cells were young cells derived from ATLL stem cells. The heating-AR and ultra-IHC detected physiological expression of the p53 protein and its probable phosphorylation by Tax in peripheral blood mononuclear cells of peripheral blood tissue specimens from HTLV-1 carriers, as well as physiological and pathological expression of the molecules involved with G1 phase progression and G1–S phase transition (E2F-1, E2F-4, DP-1, and cyclin E) in ATLL and peripheral T-cell lymphoma cells. The ultra-IHC with AR is useful for etiological pathological diagnosis of ATLL since HTLV-1 pathogenicity depends on that of Tax, and can be a useful tool for studies translating advanced molecular biology and pathology to human pathology

Experimental Evaluation of Effects of Intra-Aortic Balloon Pumping (IABP) on Ischemic Heart

The intraaortic balloon pumping (IABP) has been widely empoyed in the management of ventricular power failure. The effects of IABP were studied in a large number of reports. However, the efficacy of IABP has not been certified with reference to the severity of myocardial ischemia. Experimentally augmentation of coronary blood flow were observed on acute ischemic heart by ligation of the anterior descending artery. It has shown from the view of increased coronary blood flow that excess of 50ml/min/kg of coronary blood flow were obtained in functional reserved myocardium with ischemia. However, the efficacy of IABP on acute ischemic heart can not be precipitated by severe damage of the myocardium. The usefulness of IABP was elucidated by functional myocardial level of at least 50mmHg of LVP, 40mmHg of LVEDP and 1000mmHg/sec of max dp/dt respectivelly and it is emphasized that immediate application of IABP for cardiogenic shock allows to improve the further myocardial depression

An Experimental Functional Evaluation of End to Side Anastomosis Related to Operative Procedures of Tracheobronchial Reconstruciotn

End to side anastomosis between the trachea and the bronchus was widely employed as one of bronchial reconstructed method. However, functional evaluation undergone bronchial reconstruction did not completely display its superiority functionally. This study was undertaken to determine whether end to side anastomosis was far superior in regard to reserved pulmonary function by means of observation on changes in size of anastomotic area on xp film delineated during inspiration and exspiration simultaneously and also by intrabronchial pressure tracing. The results were as follows. 1) The creation of window defect on the tracheal wall prior to anastomosis was necessary to maintain an adequate anastomotic area. 2) The end to side anastomosis obliquely results in an excellent ventilation functionally. In contrast, the ill effects were disclosed by moderate angulation as far as exceeded 45 degree against tracheal wall owing to loss of rigidity in bronchial wall. From the present study, we concluded that end to side anastomosis obliquely with moderate degree should be avoided because of bronchial stenosis produced by bronchial collapse due to loss of supporting ability of bronchial cartilage

Clinical Evaluation of Immune Response in Patients with Cancer

Immune response was clinically evaluated in 25 patients with carcinoma compared with 26 of non cancer patients by means of lymphocyte transformation against PHA which was shown as stimulation index. In patients with cancer, stimulation index showed apparently as low as an average of 38 compared with 82 of non-cancer patients. Furthermore, the level of stimulation index was a corresponding correlation to age in which low activation was presented in the elderly. According to diseased organs, the weak response of stimulation index against PHA were observed in patients with the carcinoma of the esophagus and the lung. The response of skin test for PPD, PHA, SK-SD and candida were inhibited in patients with advanced cancer of stage III and IV compared with that of stage I and II. These responses were also suppressed in postoperative course until at least 6 months after surgery. From these results, it was noted that operative procedures provoked the induced weakness against host defense immunologically. However, it was certified that the use of immunopotentiator faciliated the activity of immune response during postoperative period for the patients with no severely advanced lung cancer of stage I and II despite of little effects for patients with advanced lung cancer of stage III and IV. It was concluded that immune response of patients with cancer was inhibited by advancing carcinoma and by operative procedures but the use of immunopotentiator was beneficial to promote the host defense during postoperative period

A Functional Evaluation of Bronchial Reconstructed Lung with Special Reference to Denervation

Bronchoplastic procedures for lung cancer were suitable operative method to reserve pulmonary function and to enlarge the resected area. However, functional evaluation is not necessarily achieved in bronchial reconstructed lung, especially with reference to denervation. In this study the influence of denervation was investigated experimentally by pulmonary perfused wedge method in which vascular tonus was directly illustrated and by measurement of oxygen saturation (Sao2) of pulmonary venous blood in which the ability of oxygen uptake was elucidated. When comparing the results of denervation with regard to operative procedures of bronchoplasty, bronchoplasty with sleeve anastomosis of pulmonary artery and autotransplantation respectively, the deteriorate effects related to bronchoplasty were not observed as compared to autotransplantation

Some Factors Concerning the Distribution of Bronchial Glands

It is well known that the secretion from bronchial glands play an important role to make the airway clean up against sticky bronchial secret. The aim of the present study was to evaluate the relationship between the functional modality of bronchial glands and occurrence of postoperative pulmonary complication due to difficulty of expectoration. However, the noteworthy development of bronchial glands was proved histologically with a distribution index (DI) in each circumstances of either the elderly more than 40 of age or existing inflammation of bronchial trees. Based on histochemical examination by means of PAS stain, the almost same attitudes in regard to magnitude of secretion were not necessarily documented even among bronchial glands with marked development. It was of note that the intimate correlation between secretory behavior of bronchial glands and development of bronchial glands was not certified in the series of this study and that secretory function of bronchial glands did not compatible with pronounced distribution and marked development of them. As a result of this study, the preventive role of bronchial glands from occurrence of postoperative pulmonary complication has not been substantiated by morphological and biochemical study

Clinical Evaluation of Immune Response in Patients with Lung Cancer

In patients with lung cancer, the immune response was observed with an analysis of various factors which mostly related to its prognosis. Its response was extremly depressed in the course of following surgery in advanced cases of stage III and IVas well as in unresectable cases for lung cancer, compared with those of stage I and II . Furthermore, it showed that the high levels of immune response were seen in those of long term survivors given OK-432 during follow-up period. It was obvious from this study that the use of OK-432 was suitable for activation of the immune reaction against host as one of the immunopotentiators. Meanwhile, from the immunological mechanism of view, the hyperactivity of immune response enable the patient to be free from recurrence of cancer for a long term following surgery, in contrast the low level of the immune response showed to be poor prognosis owing to early appearance of recurrence. Furthermore, the effectiveness in use of OK-432 was clinically presented in patients with malignant pleural effusion, which showed direct cytocidal action of OK-432 given intrapleurally with a 10 or 14 days interval

Experimental Evaluation of Tumor Growth Rate Related to Age

The differences of the growth rate of MH 134 tumor inoculated in younger or older mice were experimentally investigated in this study. The age-related tumor growth rate were evaluated as the changes of a tumor size to food pad ratio respectively. In this study, a 6 weeks-old, a 9 weeks-old and a 20 weeks-old C3H/He mice were correctly selected and prepared according to age. From the aspect of age factor in tumorbearing host, MH 134 tumor growth rate as well as survival rate after inoculation of 2.5 x 104, 2.5 x 105 and 2.5 x 106 tumor cells were simulatenously investigated in each age groups. Interestingly enough, a depressed tumor growth rate was noted in older mice in comparison with those in younger mice, whereas survival rates showed almost the same between in younger and older mice groups. While as many as 2.5 x 106 of MH 134 tumor cells were inoculated, the differences in tumor growth rate between younger and older mice were apparently pronounced. The rapid tumor growth in young mice, furthermore, were definitely denoted. Meanwhile, the improvement of survival rate in older mice had not become manifest regardless of slow growth, as compared in the two age group. Age affected some aspect of inhibitory tumor growth, whereas this assumption was not consistent with prolongation of survival time. This results reported here ensured the differences of tumor growth rate in tumorbearing host concerning age. Needless to say, the reliability of tumor resection as a treatment against cancer has been substantiated even for the elderly patients in order to enable survival rate significantly improve