Metaplastic ossification in the cartilage of the bronchus of a patient with chronic multi-drug resistant tuberculosis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Pulmonary ossification has been rarely observed in pulmonary fibrosis and in some chronic respiratory diseases such as chronic obstructive pulmonary disease. We report here a metaplastic ossification in the bronchial cartilage of a patient with multi-drug resistant tuberculosis.</p> <p>Case presentation</p> <p>We report the case of a 41-year-old Asian man from Korea with chronic multi-drug resistant tuberculosis with a rare focus of bone formation from the cartilage of a bronchus subtending an active cavity. The patient had a large multi-lobed, thick-walled cavitary tuberculosis lesion in his left upper lobe. Severe infiltration of his lymphocytes and epithelioid cells, along with some giant cells and neutrophils, was observed in the patient's bronchial wall. Desquamated bronchial epithelium and acid-fast bacilli were found inside his bronchus. A small focus of bony metaplasia was found in the cartilage of his bronchial wall. Histopathological examination confirmed calcification and showed hematopoietic cells forming in his marrow cavity.</p> <p>Conclusions</p> <p>Chronic inflammation in the lungs of our patient, caused by underlying tuberculosis, probably played a role in the development of osseous metaplasia from the associated cartilage of the bronchial wall.</p

Structures of DPAGT1 explain glycosylation disease mechanisms and advance TB antibiotic design

Summary: Protein N-glycosylation is a widespread post-translational modification. The first committed step in this process is catalysed by dolichyl-phosphate N-acetylglucosamine-phosphotransferase DPAGT1 (GPT/E.C. 2.7.8.15). Missense DPAGT1 variants cause congenital myasthenic syndrome and disorders of glycosylation. In addition, naturally-occurring bactericidal nucleoside analogues such as tunicamycin are toxic to eukaryotes due to DPAGT1 inhibition, preventing their clinical use. Our structures of DPAGT1 with the substrate UDP-GlcNAc and tunicamycin reveal substrate binding modes, suggest a mechanism of catalysis, provide an understanding of how mutations modulate activity (thus causing disease) and allow design of non-toxic “lipid-altered” tunicamycins. The structure-tuned activity of these analogues against several bacterial targets allowed the design of potent antibiotics for Mycobacterium tuberculosis, enabling treatment in vitro, in cellulo and in vivo, providing a promising new class of antimicrobial drug

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Review series Confronting the scientific obstacles to global control of tuberculosis

Tuberculosis (TB) is a major threat to global health, recently exacerbated by the emergence of highly drug-resistant forms of the disease-causing pathogen and synergy with HIV/AIDS. In 2006, the Stop TB Partnership published “The global plan to stop TB: 2006–2015, ” which set out a vision of halving the prevalence of and mortality caused by the disease by 2015, followed by eliminating the disease as a public health problem by 2050. This vision depends on the development of improved diagnostics, simpler treatment, and more effective vaccination. Recently, active translational research pipelines directed toward each of these goals have been established, but improved understanding of the fundamental biology of this complex disease will prove to be the key to radical advances in TB control

Documentation : Le projet de Code du Travail

Le projet de Code du Travail présenté en janvier dernier à la Législature de Québec avec le Bill no 5 est passé à l'histoire. Comme ce projet de législation avait une portée considerable, diverses opinions à son sujet ont été exprimées et il a été retiré. Nous publions donc, à titre documentaire, la déclaration de l'honorable Antonio Barrette, ministre du Travail, lors du retrait du Bill no 5, ainsi que ceUes de la CTCC et de la Commission Sacerdotale d'Etudes sociales. On remarquera cependant que le texte de la Commission Sacerdotale d'Etudes sociales n'avait pas été adressé aux journaux mais aux membres de l'Assemblée Législative. Les membres de cette Commission sont: l'abbé Paul-Emile Bolté, p.s.s., professeur de sciences sociales à la Faculté de Théologie de l'Université de Montréal; le R. P. Emile Bouvier, s.j., directeur de la Section des relations industrielles de l'Université de Montréal et conseiller moral de l'Association professionnelle des Industrielles; le R. P. Jacques Cousineau, s.j., conseiller moral du Conseil Central des Syndicats nationaux de Montréal et de différentes fédérations affiliées à la CTCC; l'abbé Gérard Dion, sous-directeur du Département des relations industrielles de Laval, aumônier des Associations patronales du diocèse de Québec; l'abbé Omer Genest, conseiller moral des Syndicats nationaux du diocèse de Chicoutimi et monsieur l'abbé Henri Pichette, aumônier général de la CTCC

Fig3B_AICAR

Microsoft excel file containing raw data for Fig3B AICAR

Data from: Para-aminosalicylic acid acts as an alternative substrate of folate metabolism in Mycobacterium tuberculosis

Folate biosynthesis is an established anti-infective target, and the antifolate para-aminosalicylic acid (PAS) was one of the first anti-infectives introduced into clinical practice on the basis of target-based drug discovery. Fifty years later, PAS continues to be used to treat tuberculosis. PAS is assumed to inhibit dihydropteroate synthase (DHPS) in Mycobacterium tuberculosis by mimicking the substrate p-aminobenzoate (PABA). However, we found that sulfonamide inhibitors of DHPS inhibited growth of M. tuberculosis only weakly because of their intracellular metabolism. In contrast, PAS served as a replacement substrate for DHPS. Products of PAS metabolism at this and subsequent steps in folate metabolism inhibited those enzymes, competing with their substrates. PAS is thus a prodrug that blocks growth of M. tuberculosis when its active forms are generated by enzymes in the pathway they poison

Chemical constituents and antimycobacterial studies of the leaf extracts of Pavetta crassipes K. Schum

Six known compounds; β-sitosterol, ursolic acid, methyl chlorogenate, ethyl chlorogenate, rutin and mannitol were isolated from the leaf extracts of Pavetta crassipes (Rubiaceae), a Nigerian medicinal plant used in the indigenous treatment of tuberculosis. Separation and isolation of the compounds were achieved by chromatographic techniques and the structures of isolated compounds were established by spectroscopic and chemical methods. The isolated compounds were screened for antimycobacterial activities against Mycobacterium tuberculosis H37Rv employing the green fluorescence protein reporter microplate assay and the broth microdilution method. Ursolic acid, methyl chlorogenate and ethyl chlorogenate were found moderately active in the broth microdilution assay with MICs of 200, 100 and 50 µg/ml, respectively while methyl chlorogenate and ethyl chlorogenate were active in the protein reporter microplate assay with MICs of 200 and 100 µg ml-1, respectively. The presence of antimycobacterial terpenoids and quinate esters in leaves of Pavetta crassipes provides scientific evidence for the ethnomedicinal use of the plant as a traditional anti-tuberculosis remedy