Evaluation of a Cold Staining Method for Acid-Fast Bacilli in Sputum

Comparison between the Ziehl-Neelscn staining method for acid-fast bacilli, applied with and without heating, was carried out in a controlled investigation using smears prepared from 306 sputum samples collected prior to treatment from suspected cases of pulmonary tuberculosis. Smear and culture positively were graded and the colour intensity of bacilli recorded. Results showed that the chance corrected agreement (Kappa) between Z-N and cold methods was only 78%. The sensitivity of the Z-N and cold methods were 84% and 77% respectively when compared with culture results. Assuming 10% smear positivity among symptomatics reporting to Peripheral Health Institutions (PHIs), the positive predictive value of the cold method was very low(53%). When compared to culture, the positive predictive value is 71% for the Z-N method and 57% for the cold method for a symptomatic population with 15% culture positivity. In the absence of heating. penetration of the stain was significantly reduced and consequently the number of bacilli detected was less. The inability to take the stain without heating was seen in smears from all grades of culture positive samples: thus even heavy positives were missed by the cold method. The evaluation of the cold method against the standard Z-N method highlights its limitations and demonstrates that it is not as reliable as the standard Z-N method

A role for apoptosis-inducing factor in T cell development

Apoptosis-inducing factor (Aif) is a mitochondrial flavoprotein that regulates cell metabolism and survival in many tissues. We report that aif-hypomorphic harlequin (Hq) mice show thymic hypocellularity and a cell-autonomous thymocyte developmental block associated with apoptosis at the β-selection stage, independent of T cell receptor β recombination. No abnormalities are observed in the B cell lineage. Transgenes encoding wild-type or DNA-binding–deficient mutant Aif rectify the thymic defect, but a transgene encoding oxidoreductase activity–deficient mutant Aif does not. The Hq thymic block is reversed in vivo by antioxidant treatment, and Hq T but not B lineage cells show enhanced oxidative stress. Thus, Aif, a ubiquitous protein, serves a lineage-specific nonredundant antiapoptotic role in the T cell lineage by regulating reactive oxygen species during thymic β-selection

Systemic Platelet-Activating Factor-Receptor Agonism Enhances Non-Melanoma Skin Cancer Growth

Platelet-activating factor-receptor (PAF-R) agonists are pleiotropic lipid factors that influence multiple biological processes, including the induction and resolution of inflammation as well as immunosuppression. PAF-R agonists have been shown to modulate tumorigenesis and/or tumor growth in various skin cancer models by suppressing either cutaneous inflammation and/or anti-tumoral adaptive immunity. We have previously shown that a chronic systemic PAF-R agonist administration of mice enhances the growth of subcutaneously implanted melanoma tumors. Conversely, chronic topical applications of a PAF-R agonist suppressed non-melanoma skin cancer (NMSC) in a topical chemical carcinogenesis model (dimethylbenz[a]anthracene/phorbol 12-myristate 13-acetate (DMBA/PMA)) in-part via anti-inflammatory effects. These results indicate that the context of PAF-R agonist exposure via either chronic cutaneous or systemic administration, result in seemingly disparate effects on tumor promotion. To further dissect the contextual role of PAF-R agonism on tumorigenesis, we chronically administered systemic PAF-R agonist, carbamoyl-PAF (CPAF) to mice under a cutaneous chemical carcinogenesis protocol, recently characterized to initiate both NMSC and melanocytic nevus formation that can progress to malignant melanoma. Our results showed that while systemic CPAF did not modulate melanocytic nevus formation, it enhanced the growth of NMSC tumors