The complementary role of beta-catenin in diagnosing various subtypes of renal cell carcinomas and its up-regulation in conventional renal cell carcinomas with high nuclear grades.

beta-catenin is a kind of cytoplasmic protein involved in cell adhesion and signal transduction. This study investigated its expression in various subtypes of renal cell carcinomas (RCCs) using an immunohistochemical staining method. beta-catenin expression was assessed from staining frequency and staining score. Staining score was performed by evaluating both staining percentage and intensity. All subtypes of RCCs reacted positively with beta-catenin. However, the positive frequency and staining score in papillary and chromophobe RCCs were significantly higher than those in conventional RCCs (p < 0.05). In addition, in conventional RCCs, the positive frequency and staining score of beta-catenin showed a significant difference between nuclear grades I/II and grade III (p < 0.05). Therefore, it may indicate that beta-catenin can serve as a complementary tool to distinguish conventional RCCs from chromophobe RCCs. In conventional RCCs with low nuclear grades, beta-catenin expression is generally down-regulated, while it appears to be preserved in those with high nuclear grades.

Antenatal dexamethasone administration inhibits smooth-muscle-cell DNA synthesis in pulmonary-arterial media in nitrofen-induced congenital diaphragmatic hernia in rats.

The aim of this study was to investigate the effect of antenatal glucocorticoid therapy on smooth-muscle-cell (SMC) DNA synthesis in the pulmonary arteries (PA) in a nitrofen-induced congenital diaphragmatic hernia (CDH) rat model following nitrofen administration on day 9.5 of gestation. Antenatal dexamethasone (DEX) was given intraperitoneally on days 18.5 and 19.5 of gestation. Bromodeoxyuridine (BrdU) was injected via a jugular vein into the dam 1 h before the fetuses were killed by cesarean section at term. The fetuses were divided into three groups: group I (n = 10): normal controls; group II (n = 10): nitrofen-induced CDH; group III (n = 10): nitrofen-induced CDH with antenatal DEX treatment. Immunostaining of the lungs with anti-BrdU antibody was obtained by a standard avidin-biotin complex method. The number of immunopositive cells in the PA media and adventitia were counted using an image analyzer and analyzed statistically. The number of BrdU-immunopositive cells in the media was significantly increased in group II (16.83 +/- 3.01) compared to groups I (9.16 +/- 2.20) and III (6.83 +/- 1.70) (P < 0.01). There was no significant difference between groups I and III. The number of BrdU-immunopositive cells in the adventitia was not significantly different between the three groups. Antenatal DEX treatment inhibits SMC DNA synthesis in PA media in CDH lungs. This may be a possible mechanism by which antenatal DEX prevents structural PA changes in nitrofen-induced CDH in rats.

Moxifloxacin (BAY12-8039), a new 8-methoxyquinolone, is active in a mouse model of tuberculosis.

Moxifloxacin (BAY12-8039) is a new 8-methoxyquinolone shown to be active against Mycobacterium tuberculosis in vitro. We tested moxifloxacin for activity in mice against M. tuberculosis CSU93, a highly virulent, recently isolated clinical strain. The MIC of moxifloxacin for the CSU93 strain was 0.25 microg/ml. The serum moxifloxacin concentration after oral administration in mice peaked within 0.25 h, reaching 7.8 microg/ml with doses of 100 mg/kg of body weight; the maximum concentration and the analysis of the area under the concentration-time curve revealed dose dependency. When mice were infected with a sublethal inoculum of mycobacteria and then treated with moxifloxacin at 100 mg/kg per day for 8 weeks, the log10 CFU counts in the organs of treated mice were significantly lower than those for the control group (0.6 +/- 0.2 versus 5.6 +/- 0. 3 in the lungs and 1.5 +/- 0.7 versus 4.9 +/- 0.5 in the spleens, respectively; P < 0.001 in both organs). The effectiveness of moxifloxacin monotherapy was comparable to that seen in mice receiving isoniazid alone. Combination therapy with moxifloxacin plus isoniazid was superior to that with moxifloxacin or with isoniazid alone in reducing bacillary counts in the organs studied. Using a sensitive broth-passage subculture method, we demonstrated that 8 weeks of treatment with moxifloxacin (100 mg/kg per day) or with moxifloxacin plus isoniazid (100 mg/kg and 25 mg/kg, respectively, per day) sterilized the lungs in seven of eight and in eight of eight mice, respectively. Among surviving bacilli isolated from animals infected with a high-titer inoculum and treated for 7 weeks with low-dose moxifloxacin (20 mg/kg per day), breakthrough resistance to moxifloxacin was not observed. These results indicate that moxifloxacin is highly effective in reducing M. tuberculosis infection in mice and has activity comparable to that of isoniazid. Combination therapy with moxifloxacin and isoniazid was highly effective, suggesting that moxifloxacin may be useful in multiple-drug regimens for human tuberculosis.

[Pulmonary edema associated with the Chinese medicine shosaikoto].

A 45-year-old Japanese woman presented with a high fever, a nonproductive coughing, and severe dyspnea, and was admitted to another hospital. During the week prior to hospitalization, she had been given Shosaikoto for treatment of liver dysfunction of unknown etiology. Mycoplasma pneumonitis was initially suspected, so she was treated with antibiotics (clindamycin and minocycline) and received oxygen therapy. Pulmonary insufficiency worsened rapidly, and she was transferred to our hospital. On admission, a chest roentgenogram revealed bilateral alveolar infiltrates predominantly in the medial lung fields. Furosemide and high-dose methylprednisolone were immediately administered, but hypoxemia increased. When the PaO2 was 55.7 Torr while the patient breathed 100% oxygen, mechanical ventilation with positive end-expiratory pressure (PEEP) was started. Arterial blood-gas values improved dramatically, and the chest roentgenogram became clear. Our diagnosis of noncardiogenic pulmonary edema is based on the chest-roentgenographic findings, infiltration of inflammatory cells as seen in two lung-biopsy specimens and bronchoalveolar lavage fluid, the lack of findings of heart failure on physical examination and electrocardiography, and the good clinical response to PEEP. A positive lymphocyte stimulation test in response to Shosaikoto implicated this non-traditional herbal medicine as an etiologic factor in the non-cardiogenic pulmonary edema. Shosaikoto has been identified as the cause of interstitial pneumonia or eosinophilic pneumonia, but pulmonary edema associated with Shosaikoto has not been previously described. This case suggests that methylprednisolone treatment may be insufficient for Shosaikoto-induced pulmonary edema, and that mechanical ventilation with PEEP is very effective.