Association of Bcl-2 protein expression with gallbladder carcinoma differentiation and progression and its relation to apoptosis

BACKGROUND: Bcl-2 protein is believed to play a role in neoplasia by inhibiting tumor cell apoptosis. To assess its contribution to gallbladder tumorigenesis and cancer progression, an immunohistochemical study was performed. METHODS: Fifteen adenomas and 68 adenocarcinomas were immunohistochemically and histopathologically investigated for the relation of Bcl-2 expression to p53 status, apoptosis (apoptotic index, AI), and proliferation activity (mitotic index, MI; Ki-67 labeling index, Ki-67 LI). RESULTS: The Bcl-2 score, based on intensity and extent, decreased in the order of adenoma, well-differentiated, and moderately to poorly differentiated adenocarcinoma. Early stage carcinomas demonstrated significantly higher Bcl-2 scores than their advanced counterparts (P < 0.05). On the other hand, p53 score, MI, Ki-67 LI, and AI increased in the same order. The Bcl-2 negative adenocarcinomas displayed higher AI and AI-to-MI ratios than the Bcl-2 positive group, especially in the early stage, well-differentiated lesions. A significantly positive correlation between MI(r=0.549) or Ki-67 LI(r = 0.446) and AI was observed. In early stage carcinomas, adenomatous components in the lesions were found more frequently in the polypoid lesions than in the nonpolypoid lesions (P < 0.05). CONCLUSIONS: Expression of Bcl-2 protein in gallbladder tumors appears to be positively associated with tumor cell differentiation and inversely with tumor progression. It may thus play a role in regulating carcinoma growth, especially in the early stage of tumorigenesis. It is believed that the polypoid carcinomas may arise from preexisting adenomas but the nonpolypoid carcinomas may arise as de novo carcinoma.     

Sensitivity to polyamine-induced growth arrest correlates with antizyme induction in prostate carcinoma cells

High local polyamine concentrations may suppress cell growth of primary prostatic carcinomas. When cell growth assays were conducted in defined serum-free medium, spermine inhibited the growth of poorly metastatic rat prostate carcinoma cells, causing cell cycle arrest in the G1 phase. In contrast, highly metastatic prostate carcinoma cells were resistant to the growth inhibitory activity of spermine. Ornithine decarboxylase antizyme levels, measured by Western blotting, were elevated 1-2 h after spermine treatment of spermine-sensitive cells but not spermine-resistant cells. Spermine uptake was similar in both the sensitive and resistant cell lines. These results suggest that failure to induce antizyme correlates with spermine resistance in prostate carcinoma.     

Control of Proliferation and Survival of C6 Glioma Cells with Modification of the Nerve Growth Factor Autocrine System

Nerve growth factor (NGF) plays an important physiological role in differentiation and survival of various types of neurons. Glial cells and glial tumor cells synthesize multiple neurotrophic factors including NGF and secrete them into the surrounding environment; however, the mechanisms of NGF and the significance of NGF receptors have not been studied in detail. The C6 glioma cell line can synthesize NGF, respond to exogenous application of NGF and stimulate the expression of NGF receptor in an autocrine manner. In order to determine the significance of such an NGF autocrine system, the effects of exposure to exogenous NGF and deprivation of endogenous NGF were examined in a C6 glioma cell line in vitro. Exogenous NGF significantly inhibited maintenance of the cell number and thymidine incorporation. Morphological changes, including the formation of growth cones, outgrowth of processes and cellular hypertrophy, were observed, concurrently, indicating that exogenous NGF stimulated differentiation and thereby inhibited proliferation of the cells. Deprivation of endogenous NGF with anti-NGF antibody elicited a rapid decrease in cell number and thymidine incorporation, and led almost all of the cells to death within 8 days. The protein synthesis inhibitor, cycloheximide, strongly inhibited the death of NGF-deprived cells, suggesting the involvement of an active process requiring synthesis of suicide proteins. These findings imply that the NGF autocrine system plays a significant role in regulating the differentiation and survival of C6 glioma cells, similarly to neuronal cells.     

Kawasaki disease: effect of treatment on coronary artery involvement.

Ninety-two patients with Kawasaki disease were treated with five different types of drug therapy: a steroid preparation (prednisolone), aspirin, an antibiotic, a combination of steroid plus aspirin, and a combination of steroid plus warfarin. One or two months after the onset of the disease, coronary angiography demonstrated coronary aneurysms in 20% of cases treated with an antibiotic alone, 64.7% of cases in the steroid-treated group, and 11% of those in the aspirin-treated group. These findings suggest that the steroid might act adversely to cause a progression of coronary lesions of the disease. The aspirin-treated group did not have a significantly lower incidence of coronary lesions compared with the group treated with an antibiotic alone. But in view of the fact that the direct cause of sudden death of the disease is thrombotic occlusion of a coronary artery, aspirin might act as the effective means for prevention of sudden death due to Kawasaki disease.     

Epidemiologic Studies on mumps. II. Prospective, Periodic Surveillance on Mumps in Three Different Areas

Prospective, periodical sero-epidemiological surveillance on mumps was carried out in three different populations in Aichi prefecture. 1) In a newly developed residental quarter full of big apartment buildings, where heavy population density burst has been occurring, mumps has been observed as an endemic disease. Serologically, almost all the children under six years old has experienced mumps infection in such an area. 2) In an old city with stable population dynamics, mumps outbreaks have been taken place pediodically. The results of serosurvey suggested that the periodic outbreaks occurred when more than 60–70% of the children became susceptible, regardless of seasons. 3) In a relatively isolated small town, mumps epidemics has not been observed for many years and when the disease is introduced into the community however, large outbreak develops in the town.     

Paradoxical increases in serum levels of highly chlorinated PCBs in aged women in clear contrast to robust decreases in dietary intakes from 1980 to 2003 in Japan

Objective  Exposure to polychlorinated biphenyls (PCBs) is considered to have culminated between 1950 and 1970 in Japan, and exposure through diet, the major exposure route, has decreased significantly over the last 10 years. The primary goal of the present study was to investigate the long-term trends and congener profiles of serum and dietary levels of PCBs using historical samples. Methods  Using banked samples collected in 1980, 1995, and 2003 surveys, we determined the daily intakes and serum concentrations of 13 PCB congeners (#74, #99, #118, #138, #146, #153, #156, #163, #164, #170, #180, #182, and #187) in women. Results  The total daily PCB intake [ng/day, geometric mean (geometric standard deviation)] decreased significantly from 523 (2.5) in 1980 to 63 (3.2) in 2003. The serum total PCB level (ng/g lipid) in women <40 years of age decreased significantly from 185 (1.8) in 1980 to 68 (1.8) in 2003. In contrast, the level in women >50 years of age increased significantly from 125 (1.7) in 1980 to 242 (1.7) in 2003. Specifically, the serum concentrations of hexa (#138, #146, #153, #156, #163, and #164) and hepta (#170, #180, #182, and #187) congeners increased significantly. A comparison of the serum PCB levels of women born from 1940 to 1953 revealed that their serum total PCB level was significantly higher in the 2003 survey [242 (1.7), n = 9] than in the 1995 [128 (2.0), n = 17] surveys. This increase in the total PCB level was attributable to increases in the hepta congener groups. Conclusion  Present results suggest a decreased rate of elimination of hepta congeners with aging in females, rather than a birth-generation phenomenon.     

Live varicella vaccine polarizes the mucosal adjuvant action of cholera toxin or its B subunit on specific Th1-type helper T cells with a single nasal coadministration in mice

This study was undertaken to determine whether the specific Th1- or Th2-cell response to varicella-zoster virus was induced predominantly by a mucosal adjuvant, cholera toxin, in mice. A commercially available live varicella vaccine (Oka strain) and cholera toxin or its B subunit were administered simultaneously via the nasal route. Delayed-type hypersensitivity to the Oka vaccine was induced, but the systemic neutralizing antibody response was low. The delayed-type hypersensitivity evoked after a single administration was relatively higher than that on administration three times. When spleen cells from mice immunized once with the vaccine and cholera toxin or its B subunit were restimulated with the live vaccine in vitro, there was greater thymidine uptake and production of interleukin- 2 (IL-2) than controls, but only a low level of IL-4 production. The production of IL-2 induced by the B subunit of cholera toxin was less than that by cholera toxin and a mutant of Escherichia coli enterotoxin on co-immunization with the vaccine in mice. Cholera toxin and its B subunit have been reported to induce predominantly a specific Th2-type T-cell response to various antigens. However, the Oka vaccine is an antigen that polarizes the activation of specific Th1/Th2-type T cells by cholera toxin or its B subunit to the Th1-type side. Cholera toxin and its B subunit are thus useful mucosal adjuvants for inducing cellular immunity to the Oka vaccine similar to Escherichia coli enterotoxin.     

In vitro responses to antigen stimulation: comparison between human lung parenchyma resected from asthmatic patients and non-asthmatic patients.

BACKGROUND: The airway of asthmatic patients is hyperresponsive to various stimuli in vivo. There are, however, only a few reports that compared the in vivo responsiveness of asthmatic patients and non-asthmatic subjects to those of lung parenchyma in vitro. OBJECTIVES: To compare the contractile response, release of various chemical mediators, and responsiveness to drugs in samples of lung parenchyma excised from asthma patients with those of non-asthmatic subjects. METHODS: Human lung parenchymal strips were subjected to passive sensitization with sera of 5+ RAST titer to mites. The strip was suspended in a magnus bath containing a buffer solution. Parenchymal contraction was induced by PGF2 alpha. After washing, the baseline concentrations of thromboxane B2 (TXB2), leukotriene (LT), and histamine were measured in each bath and then contraction was induced by the addition of a mite antigen. The concentrations of TXB2, LT, and histamine were measured after contraction. The inhibitory effects of TXA2 synthetase inhibitor (DP-1904) and TXA2 receptor antagonist (AA-2414) were also evaluated in both tissue samples. RESULTS: There were no significant differences between lung parenchymal tissues of asthmatic and non-asthmatic patients with regard to PGF2 alpha-induced contraction, antigen-induced contraction, release of chemical mediators, and the response to drugs. CONCLUSION: Unlike the response in vivo, there are no differences in the response to stimuli in vitro between lung parenchymal tissues of asthmatic and non-asthmatic patients.