Adjuvant interferon gamma in patients with pulmonary atypical Mycobacteriosis: A randomized, double-blind, placebo-controlled study

<p>Abstract</p> <p>Background</p> <p>High antibiotic resistance is described in atypical Mycobacteriosis, mainly by <it>Mycobacterium avium </it>complex (MAC).</p> <p>Methods</p> <p>A randomized, double-blind, placebo-controlled clinical trial was carried out in two hospitals to evaluate the effect of interferon (IFN) gamma as immunoadjuvant to chemotherapy on patients with atypical mycobacteria lung disease. Patients received placebo or 1 × 10⁶IU recombinant human IFN gamma intramuscularly, daily for one month and then three times per week up to 6 months as adjuvant to daily oral azithromycin, ciprofloxacin, ethambutol and rifampin. Sputum samples collection for direct smear observation and culture as well as clinical and thorax radiography assessments were done during treatment and one year after. Cytokines and oxidative stress determinations were carried out in peripheral blood before and after treatment.</p> <p>Results</p> <p>Eighteen patients were included in the IFN group and 14 received placebo. Groups were homogeneous at entry; average age was 60 years, 75% men, 84% white; MAC infection prevailed (94%). At the end of treatment, 72% of patients treated with IFN gamma were evaluated as complete responders, but only 36% in the placebo group. The difference was maintained during follow-up. A more rapid complete response was obtained in the IFN group (5 months before), with a significantly earlier improvement in respiratory symptoms and pulmonary lesions reduction. Disease-related deaths were 35.7% of the patients in the placebo group and only 11.1% in the IFN group. Three patients in the IFN group normalized their globular sedimentation rate values. Although differences in bacteriology were not significant during the treatment period, some patients in the placebo group converted again to positive during follow-up. Significant increments in serum TGF-beta and advanced oxidation protein products were observed in the placebo group but not among IFN receiving patients. Treatments were well tolerated. Flu-like symptoms predominated in the IFN gamma group. No severe events were recorded.</p> <p>Conclusion</p> <p>These data suggest that IFN gamma is useful and well tolerated as adjuvant therapy in patients with pulmonary atypical Mycobacteriosis, predominantly MAC. Further wider clinical trials are encouraged.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN70900209.</p

The Mouse Homeobox Gene, Gbx2: Genomic Organisation and Expression in Pluripotent Cells in Vitro and in Vivo

The Gbx2 homeodomain is widely conserved in metazoans. We investigated the mouseGbx2locus by isolation and characterization of genomic clones and by physical localization to the genome. TheGbx2gene contained a single intron that separated the proposed functional protein domains. This organization was conserved with humanGBX2.Physical localization ofGbx2to Chromosome 1C5–E1 indicated that the genomic relationship between the linkedGbx2andEn1genes differs between mouse and human, making it unlikely to be of functional significance. We also extended the known expression pattern ofGbx2beyond the gastrulation stage embryo and the developing CNS to pluripotent cellsin vitroandin vivo. Gbx2expression was demonstrated in undifferentiated embryonic stem cells but was downregulated in differentiated cell populations. In the embryo,Gbx2expression was detected before primitive streak formation, in the inner cell mass of the preimplantation embryo.Gbx2is therefore a candidate control gene for cell pluripotency and differentiation in the embryo