The cathepsin D is a lysosomal protease secreted in excess by breast cancer cells. The function of this enzyme is degradation of the extracellular matrix and proteoglycan. It is induced by estrogens in estrogen receptor positive breast cancer cell lines. On the basis of this, cathepsin D expression in breast cancer cells seems to be correlated with the prognosis. But there is debates in its prognostic significance. Relationship between cathepsin D expression and other prognostic factors of breast cancer was studied. We investigated 51 cases of invasive ductal cell carcinoma of breast removed by open biopsy or mastectomy. All cases were fixed in formalin and embedded in paraffin. We used 46-KD intermediate form of the enzyme for cathepsin D expression on immunohistochemical stain. We observed no significant correlation with age, stage, histologic grade, lymphatic invasion, and estrogen receptor status. Cathepsin D may be an independent factor which is not related with other prognostic factors, especially estrogen receptor status.
Biopsy ; Breast Neoplasms

BACKGROUND: Viral myocarditis is considered as a cause of dilated cardiomyopathy. At present, two pathogenic mechanisms may be involved in the pathogenesis of viral myocarditis and subsequent cardiomyopathy. First, the virus infection of myocyte may directly lead to either cell death or persistent metabolic dysfunction. Second, virus-induced immune or autoimmune mechanism may play a role. METHODS: To test the therapeutic efficacy of immunosuppression with cyclophophamide(CYP) on coxsackievirus B3(CB3) myocarditis, 10-14 week-old Balb/c mice were inoculated with 4000 plaque-forming units of CB3. In experiment 1, CYP (100mg/kg/day subcutaneous injection, s.c) was administrated daily on days 1-7(group 2, n=16). In experiment 2, CYP 30mg/kg/day s.c(group 3, n=32) or CYP 100mg/kg/day s.c(group 4, n=32) were administrated on days 8-14. The animals of infected controls(group 1, n=26) and group 2, 3, 4 were dissected at days 4, 7, 15, 22 and spleen, heart, thymus and body weights were measured. RESULTS: In experiment 1. survival rate in group 2 on day 7, 15 were low compared with group 1(85%, 0% vs 100%, p<0.05). and myocardial virus titers in group 2 on day 4 was 50 times, and on day 7, 1000 times higher compared with group 1, Histologically, on day 7, focal cellular infiltrations were prominent findings in group 1, but diffuse myocardial necrosis without cellular infiltration were observed in group 2. In experiment 2, survival rate, cardiac histopathology myocardial virus titer and serum neutralizing antibody titers did not differ among groups 1, 3 and 4. In experiment 1 and 2, the spleen-to-body-weight and thymus-to-body-weight ratios were significantly lower in CYP treated groups than those in controls and marked cellular depletions in spleens and thymus were observed in CYP treated groups. CONCLUSIONS: As the results of above, it can be concluded that the immunosuppression during viremic phase of murine viral myocarditis aggravated the myocardial necrosis, and during aviremic phase, the administration of CYP didnot affect the process of viral myocarditis. Thus, direct viral mechanisms in the production of cardiomyocyte injury in CB3-infected mice appear to bo more important than cell mediated immune mechanism. To understand relevant pathogenic mechanisms of clinical myocarditis and dilated cardiomyopathy resulting from viral infection, the experimental study expanding into nonmurine animals and into various models using other infectious agents may be required.
Animals ; Antibodies, Neutralizing ; Body Weight ; Cardiomyopathies ; Cardiomyopathy, Dilated ; Cell Death ; Cyclophosphamide* ; Heart ; Immunosuppression ; Injections, Subcutaneous ; Mice ; Muscle Cells ; Myocarditis* ; Myocytes, Cardiac ; Necrosis ; Spleen ; Survival Rate ; Thymus Gland ; Viral Load

BACKGROUND: Severe acute lung injury(ALI), also known as the adult respiratory distress syndrome(ARDS), is a heterogenous nature of dynamic and explosive clinical synrome that exacts a mortality of approximately 50%. Endotoxin(ETX) is an abundant component of the outer membrane of gram-negative bacteria capable of inducing severe lung injury in gram-negative sepsis and gram-negative bacterial pneumonia, which are among the most common predisposing causes of ARDS. The influx of PMNs into airway tissue is a pathological hallmark of LPS-induced lung injury. And th3re is a substantial evidence suggesting that cytokines are important mediators of lung injury in gram-negative sepsis. However, the kinetics of phagocytes and cytokines by an exact time sequence and their respective pathogenic importance remain to be elucidated. This study was performed to investigate the role of phagocytes and proinflammatory cytokines in ETX-induced ALl through a time course of changes in the concentration of protein, TNFa and IL-6, and counts of total and its differential cells in BALF. The consecutive histologic findings were also evaluated. METHOD: The experimental animals, healthy male Sprague-Dawley, weighted 200+/-50g, were divided into controland ALI-group. ALI was induced by an intravenous administration of ETX, 5mg/kg. Above mentioned all parameters were examined at 0(control), 3, 6, 24, 72 h after administration of ETX. TNFa and IL-6 conc. in BALE were measured by a bioassay. RESULTS: The protein concentration and total leukocyte count(TC) in BALF was significantly increased at 3h compared to controls(p<0.05). The protein conc. was significantly elavated during observation period, but TC was significantly decreased at 72h(p<0.05 vs. 24h). There was a close relationship between TC and protein cone. in BALF(r = 0.65, p <0.001). The PMN and monocyte count was well correlated with TC in BALF, and the correlation of PMN(r=0.97, p<0.001) appeared to be more meaningful than that of monoeyte(r = 0.61, p<0.001). There was also a significant correlation between protein cone. and PMN or monocyte count in BALF(PMN vs. monocyte r = 0.55, p<0.005 vs. r = 0.64, p<0.001). The count of monocyte was significantly elavated during observation period though a meaningful reduction of PMN count in BALF at 72h, this observation suggested that monocyte may, at least, partipate in the process of lung injury steadly. In this sudy, there was no relationship between IL-6 and TNFt conc., and TNFa but not IL-6 was correlated with TC(r 0.61, p <0.05) and monocyte(r = 0.67, p<0.05) in BALF only at 3, 6h after ETX introduced. In particular, the IL-6 cone. increased earlier and rapidly peaked than TNFz cone. in BALF. In histologic findings, the cell counts of lung slices were increased from 3 to 72h(p<0.001 vs. NC). Alveolar wallthickness was increased from 6 to 24h(p<0.001 vs. NC). There was a significant correlation between the cell counts of lung slices and alveolar wall-thickness(r= 0.61, p<0.001). This result suggested that the cellular infiltrations might be followed by the alterations of interstitium, and the edematous change of alveolar wall might be most rapidly recovered to its normal condition in the process of repair. CONCLUSION: We concluded that although the role of PMIN is partly certain in ETX-induced ALI, it is somewhat inadequate to its known major impact on ALL Alveolar macrophage and/or non-immune cells such as pulmonary endothelial or epithelial cells, may be more importantly contributed to the initiation and perpetual progression of ETX-induced ALI. The IL-6 in ETX-induced ALI was independent to TNFa, measured by a bioassay in BALF. The early rise in IL-6 in BALF implies multiple origins of the IL-6.
Acute Lung Injury* ; Administration, Intravenous ; Adult ; Animals ; Biological Assay ; Cell Count ; Cytokines ; Epithelial Cells ; Gram-Negative Bacteria ; Humans ; Interleukin-6 ; Kinetics ; Leukocytes ; Lung ; Lung Injury ; Macrophages, Alveolar ; Male ; Membranes ; Monocytes ; Mortality ; Phagocytes* ; Pneumonia, Bacterial ; Rats, Sprague-Dawley ; Sepsis