The Mycobacterium tuberculosis gene Rv3232c/MT3329 (ppk2) encodes a class II polyphosphate kinase, which hydrolyzes inorganic polyphosphate (poly P) to synthesize GTP. We assessed the role of ppk2 in M. tuberculosis poly P regulation, antibiotic tolerance, and virulence. A ppk2-deficient mutant (ppk2::Tn) and its isogenic wild-type (WT) and complemented (Comp) strains were studied. For each strain, the intrabacillary poly P content, MIC of isoniazid, and growth kinetics during infection of J774 macrophages were determined. Multiplex immunobead assays were used to evaluate cytokines elaborated during macrophage infection. The requirement of ppk2 for M. tuberculosis virulence was assessed in the murine model. The ppk2::Tn mutant was found to have significantly increased poly P content and a 4-fold increase in the MIC of isoniazid relative to the WT and Comp strains. The ppk2::Tn mutant showed reduced survival at day 7 in activated and naive J774 macrophages relative to the WT. Naive ppk2::Tn mutant-infected macrophages showed increased expression of interleukin 2 (IL-2), IL-9, IL-10, IL-12p70, and gamma interferon (IFN-γ) relative to WT-infected macrophages. The ppk2::Tn mutant exhibited significantly lower lung CFU during acute murine infection compared to the control groups. ppk2 is required for control of intrabacillary poly P levels and optimal M. tuberculosis growth and survival in macrophages and mouse lungs.

In a previous study, we found tumor-associated tissue eosinophilia (TATE) to be a favorable prognostic indicator for squamous cell carcinoma of the head and neck (p less than 0.05). The present expanded study was undertaken to confirm this finding. The pathology of 120 head and neck tumors was examined for histologic features suggestive of poor prognosis. Ten descriptive histopathologic variables, including two malignancy grading scales, were correlated with DNA flow cytometric data and clinical outcome. No correlation was found between the malignancy grading scales and DNA flow cytometric data or clinical outcome. The present expanded study confirmed with greater statistical significance (p less than 0.001) that high-grade TATE is a favorable prognostic indicator for head and neck cancer. Furthermore, high-grade TATE was associated with the absence of distant metastasis (p less than 0.05). Using a stepwise logistic regression analysis of the clinicopathologic variables in the study, high-grade TATE was the most influential variable affecting clinical outcome, followed by border, stage, and perineural invasion. We conclude that the grade of TATE is a significant prognostic indicator for head and neck cancer. The significance and possible role of the eosinophil in the tumor-host interaction are discussed.

Basal cell carcinoma is the most common ofthe cutaneous mal ignancies, accounting for 65 to 75 % of all skin cancers. The natural history ofthis disease is one ofchronic local invasion. Metastatic basal cell carcinoma is a rare clinical entity, with a reported incidence ofonly 0.002 8 to 0.5%. Approximately 85 % of all metastat ic basal cell carcinomas arise in the head and neck region. We p resent a case ofbasal cell carcinoma that spread to the parotid gland in a man who had multiple lesions on his scalp and f ace. We also review the literature on metastatic basal cell carcinoma of the head and neck, and we discuss its epidemiology, etiology, histopath ology, and treatment. AlcanPHARMACEUTICALS YOUR COMBINATION THERAPY FOR OTITIS EXTERNA ' CIPRO' is a registered trademark of Bayer AG. Licensed by Bayer AG. Please tum page for brief summary of prescribing informalion. 2000 Alcon laboratories, Inc. ;/00 CflCOO;OOJA Primed in U. S.A, @ Convenience and compliance of 3-2-7 3 drops, 2 times/day for 7 days @ Delivers significantly shorter time-to-end of ear pain than does a fluoroquinolone with no steroid' @ Safe for patients 1 year of age and older @ Thimerosal-and neomycin-free @ The potent antibacterial activity of CIPRO e * Douse the pain with. CIPRO e HC OTIC @ The first and only fluoroquinolone/steroid combination for otitis externa CIPRo-HC cĩ ml l u X3 Ciu~LĨ n~~~~r o~~r t l s~nt ĩ sus~~nsĩn