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Biomedical subjects

L M Rocha

Publications and source records attributed to L M Rocha.

8 recordsLinked to original sources

Inhibition of isoniazid-induced expression of Mycobacterium tuberculosis antigen 85 in sputum: potential surrogate marker in tuberculosis chemotherapy trials.

Mycobacterium tuberculosis antigen 85 is induced in vitro by isoniazid (INH); its sustained induction in sputum during tuberculosis (TB) therapy predicts relapse. In this trial, rifampin or rifalazil inhibited the induction of sputum antigen 85 by INH in a dose-dependent fashion. This approach may facilitate the evaluation of new TB drugs.

Acyltransferases↗

Safety and bactericidal activity of rifalazil in patients with pulmonary tuberculosis.

Rifalazil, also known as KRM-1648 or benzoxazinorifamycin, is a new semisynthetic rifamycin with a long half-life of approximately 60 h. Rifalazil has potent bactericidal activity against Mycobacterium tuberculosis in vitro and in animal models of tuberculosis (TB). Prior studies in healthy volunteers showed that once-weekly doses of 25 to 50 mg of rifalazil were well tolerated. In this randomized, open-label, active-controlled phase II clinical trial, 65 subjects with sputum smear-positive pulmonary TB received one of the following regimens for the first 2 weeks of therapy: 16 subjects received isoniazid (INH) (5 mg/kg of body weight) daily; 16 received INH (5 mg/kg) and rifampin (10 mg/kg) daily; 17 received INH (5 mg/kg) daily plus 10 mg of rifalazil once weekly; and 16 received INH (5 mg/kg) daily and 25 mg of rifalazil once weekly. All subjects were then put on 6 months of standard TB therapy. Pretreatment and day 15 sputum CFU of M. tuberculosis were measured to assess the bactericidal activity of each regimen. The number of drug-related adverse experiences was low and not significantly different among treatment arms. A transient decrease in absolute neutrophil count to less than 2,000 cells/mm(3) was detected in 10 to 20% of patients in the rifalazil- and rifampin-containing treatment arms without clinical consequences. Decreases in CFU counts were comparable among the four treatment arms; however, the CFU results were statistically inconclusive due to the variability in the control arms. Acquired drug resistance did not occur in any patient. Studies focused on determining a maximum tolerated dose will help elucidate the full anti-TB effect of rifalazil.

Adolescent↗

Syntactic autonomy. Why there is no autonomy without symbols and how self-organizing systems might evolve them.

Two different types of agency are discussed that are based on dynamically coherent and incoherent couplings with an environment, respectively. I propose that until a private syntax (syntactic autonomy) is discovered by dynamically coherent agents, there are no significant or interesting types of closure or autonomy. When syntactic autonomy is established, then, because of a process of description-based selected self-organization, open-ended evolution is enabled. At this stage, in addition to dynamics, agents depend on localized, symbolic memory, thus adding a level of dynamic incoherence to their interaction with the environment. Furthermore, it is the appearance of syntactic autonomy that enables much more interesting types of closures among agents sharing the same syntax. To investigate how we can study the emergence of syntax from dynamic systems, experiments with cellular automata leading to emergent computation that solves nontrivial tasks are discussed. RNA editing is also mentioned as a process that may have been used to obtain a primordial biological code necessary for open-ended evolution.

Biological Evolution↗

Evolution with material symbol systems.

Pattee's semantic closure principle is used to study the characteristics and requirements of evolving material symbols systems. By contrasting agents that reproduce via genetic variation with agents that reproduce via self-inspection, we reach the conclusion that symbols are necessary to attain open-ended evolution, but only if the phenotypes of agents are the result of a material, self-organization process. This way, a study of the inter-dependencies of symbol and matter is presented. This study is based first on a theoretical treatment of symbolic representations, and secondly on simulations of simple agents with matter-symbol inter-dependencies. The agent-based simulations use evolutionary algorithms with indirectly encoded phenotypes. The indirect encoding is based on Fuzzy Development programs, which are procedures for combining fuzzy sets in such a way as to model self-organizing development processes.

Algorithms↗

Membranoproliferative glomerulonephritis associated with a mixed-cell germinal ovary tumor.

We describe a patient with membranoproliferative glomerulopathy associated with a mixed-cell germinal ovary tumor (embryonal and dysgerminoma components). Advanced renal failure ensued without remission of nephrotic syndrome after surgery. Five other cases of ovary tumor associated with glomerulopathy and reported in the literature are reviewed. The association between membranoproliferative glomerulonephritis and mixed-cell germinal ovary tumor has not been previously reported.

Adolescent↗