Daunomycin is a new antibiotic in the anthracycline group obtained from Streptomyces peucetius. It consists of a pigmented aglycone (daunomycinone) in glycoside linkage with an amino sugar (daunosamine). Differences in the biological effects of daunomycin, which reacts with DNA, and actinomycin D which complexes with DNA in a different manner to inhibit RNA production, are discussed. The toxic effects of daunomycin are a severe local reaction if the drug extravasates, bone marrow depression resulting in leucopenia, anemia, thrombocytopenia and bleeding, fever, oral ulcers and alopecia. In patients receiving maintenance doses of daunomycin the development of tachypnea, tachycardia pulmonary insufficiency, heart failure and hypotension possibly is associated with daunomycin but the evidence is unclear. Sixty per cent of children with leukemia obtained brief complete or partial hematological remissions from a single course of daunomycin. The remission could be prolonged by maintenance therapy. Daunomycin is temporarily effective in some cases of neuroblastoma, reticulum cell sarcoma and rhabdomyosarcoma.

The gene for the extracellular alpha antigen of Mycobacterium bovis BCG was cloned by using a single probe restricted to G or C in the third position. This technique should have great potential for the isolation of mycobacterial antigen genes. The gene analysis revealed that the alpha antigen gene encoded 323 amino acid residues, including 40 amino acids for signal peptide followed by 283 amino acids for mature protein. This is the first report on the structure of the mycobacterial signal peptide. The promoter-like sequence and ribosome-binding site were observed upstream of the open reading frame. In the coding region, the third position of the codon showed high G + C content (86%). The gene was expressed as an unfused protein in Escherichia coli by using an E. coli expression vector. This protein, which reacted with polyclonal antibody raised against alpha antigen from Mycobacterium tuberculosis, would be applicable to the immunodiagnosis of tuberculosis.

During previous cooperative numerical taxonomic studies of slowly growing mycobacteria, the International Working Group on Mycobacterial Taxonomy described a number of strains whose taxonomic status was ambiguous. A new study of DNA, RNA, and proteins from 66 of these organisms was performed to correlate their properties with phenotypic clustering behavior; the results of this study permitted 5 1 of the strains studied to be assigned to known species. The methods used to characterize the semantides included nucleotide sequencing and assessment of levels of semantide relatedness by affinity binding techniques, including whole DNA-DNA hybridization, probe hybridization, and antibody binding. There was good overall agreement between the phenotypic and chemotaxonomic clusters and the groups of organisms identified by semantide analyses. Our results supported the conclusion that we should continue to rely on polyphasic taxonomy to provide satisfactory systematic resolution of members of the genus Mycobacterium. We identified no single 16s rRNA interstrain nucleotide sequence difference value that unequivocally defined species boundaries. DNA-DNA hybridization remains the gold standard, but common resources are needed to permit DNA-DNA hybridization analyses to be made available to laboratories that are not prepared to use this technology. One of the large novel clusters which we studied corresponds to the recently described species Mycobacterium interjecturn, a pathogen that resembles the ilonpathogen Mycobacterium gurdonae phenotypically, We also identified strains that appear to represent ribovars of Mycobacterium intracellulare which do not react with the commercial diagnostic probes that are currently used for identification of this species. Other branches or clusters consisted of too few strains to permit a decision about their taxonomic status to be made.Approximately 17 years ago the International Working Group on Mycobacterial Taxonomy (IWGMT) began a cooperative open-ended study in which phenotypically unusual strains of s l o~l y growing mycobacteria were collected on a continuing basis. These strains were distributed to participants in the open-ended study for characterization by a broad range of predominantly phenotypic tests, and at intervals the data obtained were subjected to numerical taxonomic (NT) analyses (29-32). The purpose of studying an expanding set of cultures was to characterize slowly growing mycobacterial strains that either represented uncommonly encountered species that had not been represented in previous cooperative studies (10, 25, 28) or belonged to clusters of previously unrecognized taxa. These analyses yielded expanded phenotypic characterizations of members of some clusters that had not been thoroughly characterized before, such as the clusters that included the type strains of Mycobacterium simiae, Mycobacterium szulgai, Mycobacterium asiaticum, and Mycobacterium malmoense (3 1). However, some individual strains and phenotypic clusters emerged that exhibited no unequivocal aff...

The gene for the extracellular a antigen of Mycobacterium kansasii was cloned by using the a-antigen gene fragments of M. bovis BCG as probes. Gene analysis revealed that this gene encodes 325 amino acid residues, including 40 amino acids for the signal peptide, followed by 285 amino acids for the mature protein. A comparison of the nucleotide sequences of the genes isolated from these two mycobacterial species showed that the levels of DNA and amino acid homology were 84.8 and 89.1%, respectively. The hydropathy profiles were also compared, and two highly changed hydrophilic regions were observed, which might account for the antigenic diversity of this antigen or its acquirement of antigenic specificity. 550 on August 10, 2020 by guest http://iai.asm.org/ Downloaded from

To clarify the correlation of cytokine level with the severity and prognosis of children with the hemophagocytic syndrome, we analyzed serum interleukin-1 (IL-1) and tumor necrosis factor (TNF) levels in 26 children with either the virus-associated hemophagocytic syndrome (VAHS, n = 12) or malignant histiocytosis (MH, n = 14). When compared to healthy controls, 13 children had an elevated IL-1 ( ≥ 20 pg/ml) and 21 children had an elevated TNF ( ≥10 pg/ml) level at diagnosis. There was, however, no significant difference in the frequency of these high levels between the patients with VAHS and MH. Neither IL-1 nor TNF levels correlated with other clinical or laboratory findings in either VAHS or MH. Two of the 12 patients with VAHS died of an intracranial hemorrhage and 7 of the 14 patients with MH died despite chemotherapy. The MH patients who had a high TNF level (≥50 pg/ml) had a poorer prognosis than those with a low TNF level ( < 50 pg/ml; p < 0.01). In MH patients, other parameters, such as coagulopathy and lactic dehydrogenase, ferritin and IL-1 levels, did not correlate with prognosis. In 3 patients (2 with VAHS and 1 with MH) analyzed periodically, the change in TNF level was closely associated with the clinical progression or regression of the diseases. Serum cytokine levels may thus be monitored not only for predicting the severity and prognosis of VAHS or MH but also for determining the indications for or timing of chemotherapy. Moreover, TNF may play an important role in the progression of VAHS and MH.