The association of genetic groups 1, 2, and 3 of Mycobacterium tuberculosis with pulmonary and extra-pulmonary tuberculosis

Objective. To investigate the association of the three major genetic groups of Mycobacterium tuberculosis with pulmonary and extra-pulmonary tuberculosis in clustered and non-clustered TB cases in the Houston area. ^ Study design. Secondary analysis of an ambi-directional study. ^ Study population. Three hundred fifty-eight confirmed cases of tuberculosis in the Houston that occurred between October 1995 and May 1997, who had been interviewed by the Houston T13 Initiative staff at Baylor College of Medicine, and whose isolates have had their DNA fingerprint and genetic group determined. ^ Exclusions. Individuals whose mycobacterial genotype was unknown, or whose data variables were unavailable. ^ Source of data. Laboratory results, patient interviews, and medical records at clinics and hospitals of the study population. ^ Results. In clustered cases, the majority of both, pulmonary and extra-pulmonary TB cases were caused by genetic group 1. Independent factors were assessed to determine the interactions that may influence the site of infection or increase the risk for one site or another. HIV negative males were protected against extra-pulmonary TB compared to HIV negative females. Individuals ages 1–14 years were at higher risk of having extra-pulmonary TB. Group 3 organisms were found less frequently in the total population in general, especially in extra-pulmonary disease. This supports the evidence in previous studies that this group is the least virulent and genetically distinct from the other two groups. Group 1 was found more frequently among African Americans than other ethnic groups, a trend for future investigations. ^ Among the non-clustered cases, group 2 organisms were the majority of the organisms found in both sites. They were also the majority of organisms found in African Americans, Caucasians, and Hispanics causing the majority of the infections at both sites. However, group 1 organisms were the overwhelming majority found in Asian/Pacific Islander individuals, which may indicate these organisms are either endemic to that area, or that there is an ethnic biological factor involved. This may also be due to a systematic bias, since isolates from individuals from that geographic region lack adequate copies of the insertion sequence IS6110, which leads to their placement in the non-clustered population. ^ The three genetic groups of Mycobacterium tuberculosis were not found equally distributed between sites of infection in both clustered and non-clustered cases. Furthermore, these groups were not distributed in the same patterns among the clustered and non-clustered cases, but rather in distinct patterns. ^

UPTAKE, METABOLISM, AND METABOLIC EFFECTS OF THE ANTITUMOR TRICYCLIC NUCLEOSIDE, 3-AMINO-1, 5-DIHYDRO-5-METHYL-1-BETA-D-RIBOFURANOSYL-1, 4, 5, 6, 8 PENTAAZAACENAPHTHYLENE

The uptake, metabolism, and metabolic effects of the antitumor tricyclic nucleoside (TCN, NSC-154020) were studied in vitro. Uptake of TCN by human erythrocytes was concentrative, resulting mainly from the rapid intracellular phosphorylation of TCN. At high TCN doses, however, unchanged TCN was also concentrated within the erythrocytes. The initial linear rate of TCN uptake was saturable and obeyed Michaelis-Menten kinetics. TCN was metabolized chiefly to its 5'-monophosphate not only by human erythrocytes but also by wild-type Chinese hamster ovary (CHO) cells. In addition, three other metabolites were detected by means of high-performance liquid chromatography. The structures of these metabolites were elucidated by ultraviolet spectroscopy, infrared spectroscopy, mass spectrometry, and further confirmed by incubations with catabolic enzymes and intact wild-type or variant CHO cells. All were novel types of oxidative degradation products of TCN. Two are proposed to be (alpha) and (beta) anomers of a D-ribofuranosyl nucleoside with a pyrimido{4,5-c}pyridazine-4-one base structure. The third metabolite is most likely the 5'-monophosphate of the (beta) anomer. A CHO cell line deficient in adenosine kinase activity failed to phosphorylate either TCN or the (beta) anomer. No further phosphorylation of the 5'-monophosphates by normal cells occurred. Although the pathways leading to the formation of these TCN metabolites have not been proven, a mechanism is proposed to account for the above observations. The same adenosine kinase-deficient CHO cells were resistant to 500 (mu)M TCN, while wild-type cells could not clone in the presence of 20 (mu)M TCN. Simultaneous addition of purines, pyrimidines, and purine precursors failed to reverse this toxicity. TCN-treatment strongly inhibited formate or glycine incorporation into ATP and GTP of wild-type CHO cells. Hypoxanthine incorporation inhibited to a lesser degree, with the inhibition of incorporation into GTP being more pronounced. Although precursor incorporation into GTP was inhibited, GTP concentrations were elevated rather than reduced after 4-hr incubations with 20 (mu)M or 50 (mu)M TCN. These results suggested an impairment of GTP utilization. TCN (50 (mu)M) inhibited leucine and thymidine incorporation into HClO(,4)-insoluble material to 30-35% of control throughout 5-hr incubations. Incorporation of five other amino acids was inhibited to the same extent as leucine. Pulse-labeling assays (45 min) with uridine, leucine, and thymidine failed to reveal selective inhibition of DNA or protein synthesis by 0.05-50 (mu)M TCN; however, the patterns of inhibition were similar to those of known protein synthesis inhibitors. TCN 5'-monophosphate inhibited leucine incorporation by rabbit reticulocyte lysates; the inhibition was 2000 times less potent than that of cycloheximide. The 5'-monophosphate failed to inhibit a crude nuclear DNA-synthesizing system. Although TCN 5'-monophosphate apparently inhibits purine synthesis de novo, its cytotoxicity is not reversed by exogenous purines. Consequently, another mechanism such as direct inhibition of protein synthesis is probably a primary mechanism of toxicity. ^

Der Austritt aus der Synagogengemeinde : das Gesetz u. dessen Berathung im Hause d. Abgeordneten in 1., 2. u. 3. Lesung, nach d. stenogr. Berichten d. Abgeordnetenhauses zsgest. u. mit e. Vorw. vers.

von S. Meyer

Grundsaetze des Revisionismus : aus den Resolutionen der 1., 2. u. 3. Weltkonferenz d. Revisionistischen Union

hrsg. vom Zentralbuero d. Union d. Zionisten Revisionisten

Psalm I : verses 1, 2 and 3 ; chorus and solo with English and German words

composed by A. Kaiser

Δ I = 1 / 2 rule for kaon decays derived from QCD infrared fixed point

This article gives details of our proposal to replace ordinary chiral SU(3)L×SU(3)R perturbation theory χPT3 by three-flavor chiral-scale perturbation theory χPTσ. In χPTσ, amplitudes are expanded at low energies and small u,d,s quark masses about an infrared fixed point αIR of three-flavor QCD. At αIR, the quark condensate ⟨q¯q⟩vac≠0 induces nine Nambu-Goldstone bosons: π,K,η, and a 0++ QCD dilaton σ. Physically, σ appears as the f0(500) resonance, a pole at a complex mass with real part ≲ mK. The ΔI=1/2 rule for nonleptonic K decays is then a consequence of χPTσ, with a KSσ coupling fixed by data for γγ→ππ and KS→γγ. We estimate RIR≈5 for the nonperturbative Drell-Yan ratio R=σ(e+e−→hadrons)/σ(e+e−→μ+μ−) at αIR and show that, in the many-color limit, σ/f0 becomes a narrow qq¯ state with planar-gluon corrections. Rules for the order of terms in χPTσ loop expansions are derived in Appendix A and extended in Appendix B to include inverse-power Li-Pagels singularities due to external operators. This relates to an observation that, for γγ channels, partial conservation of the dilatation current is not equivalent to σ-pole dominance.

Allerunterthänigst-Rechts begründete Additional-Anzeig Ad Exhibitum de 23. Julij nup. und Bitt pro clem.mè demandanda[m] illius celere Relatione, Petitóque deferendo : An Die Römis. Kayserl. ... Majestät [et]c. ; In Sachen Judenschafft zu Franckfurth Contra E. E. Magistrat daselbst ; Bey höchst-preißlichen Reichs-Hof-Rath Den 28. Sept. 1714 übergeben ; Mit Beylagen Num. 1, 2 & 3 ; Rescripti das Bau-Weesen betreffend

Intervenientischer Burgerschafft

Ms. Ff. Mus. 1339 - Am 2. Advent : Seyd wacker allezeit, und bethet, daß ihr p. ; C. A. T. B., 2 oboe, 2 violini, 1 viola, violoncello et organo

von Teleman[n]. [Textverf.: Gottfried Simonis]