Immunosuppression in cervical cancer with special reference to arginase activity.

INTRODUCTION: Cervical cancer is characterized by an immunosuppressive microenvironment and a Th2-type cytokine profile. Expression of arginase (ASE), the enzyme that converts L-arginine into L-ornithine and urea, is stimulated by Th2-type cytokines. OBJECTIVE: To assess the association of ASE activity and L-Arg metabolism products with cervical cancer. METHODS: Sera of 87 and 41 women with histologically confirmed by colposcopy-directed biopsy SCC and CIN3 respectively and 79 with normal cytology or Low-Grade Squamous Intraepithelial Lesion (LSIL), were evaluated. Cytokines were measured using Milliplex Human cytokine/chemokine kit. Arginase (ASE) activity was determined using an enzymatic assay. Levels of L-arginine, L-ornithine, putrescine and spermine were determined by HPLC. RESULTS: Significantly higher levels of ASE activity were observed in women with CIN3 (age-adjusted OR: 24.3; 95%CI: 3.82-155) and SCC (AOR: 9.8; 95%CI: 2.34-40.8). As expected, possibly due to high levels of ASE activity, higher levels of l-Arg were negatively associated with CIN3 (AOR: 0.03; 95%CI: 0.004-0.19) and SSC (AOR: 0.06; 95%CI: 0.02-0.24). Consistent with the role of ASE in the conversion of L-arginine to L-ornithine and polyamine production therefrom, women with cervical cancer had higher levels of spermine and putrescine. A correlation analysis revealed a significant albeit weak relationship between high levels of IL-10 and high levels of ASE (Pearson r=0.32, p-value=0.003) in women with cervical cancer. CONCLUSION: This study indicates that ASE activity and L-Arg degradation mechanisms of immunosuppression are present in cervical cancer. The results foster research in the design of possible strategies to inhibit ASE activity for therapy of cervical cancer.

Molecular and clinical epidemiology of endemic acinetobacter antiratus infections in an urban teaching hospital - abstract

Acinetobacter anitratus is an important nosocomial pathogen with an environmental reservoir. An increased rate of isolations from hospitalised patients prompted this study. Infections were identified in 62 of 81 patients (76 percent), aged 2 months to 95 years in whom A. anitratus was isolated. Seventy-one episodes occurred in the summer and spring versus 10 in the winter and fall of 1990 to 1992 (p<0.0000001). Thirty percent of the patients had pneumonia, 7 percent had peritonitis, and urinary tract infections occurred in 23 percent of patients. The organism was also isolated from deep abscesses and cases of tracheobronchitis. The use of ventilators and continuous ambulatory peritoneal dialysis were significant contributors to the occurrence of infection (OR 11.5, p<0.0004; p<0.000005, respectively). Other features included recent antibiotic use (70 percent), recent hospitalisation (37 percent), Foley catheters (69 percent), total parenteral nutrition (39 percent), angiography (37 percent), chest tubes (25 percent), tracheostomy (23 percent) and epidural anaesthesia (9 percent). Ninety-seven percent had underlying illnesses, 63 percent had major surgery and 34 percent were immunosuppressed. Fifty-five percent of the patients acquired the organism in ICU, and 12 (15 percent) patients died. DNA fingerprinting, using pulsed-field gel electrophoresis (PFGE) of the whole cell DNA digested with Sma 1, revealed 6 PFGE banding patterns among 27 isolates (8 isolates with a common pattern were clustered in the Surgical ICU) and distinct patterns in 44. A.anitratus causes device-associated nosocomial infections in severely ill patients with marked seasonal variation (AU)