Advances in Mycobacterium tuberculosis structural genomics: investigating potential chinks in the armor of a deadly pathogen.

The waning effectiveness of established tuberculosis treatments due to the rise of multi and extensively drug-resistant strains of Mycobacterium tuberculosis, coupled with the synergism of HIV infection, demands basic research efforts to inform focused drug development programs. Structural genomics projects provide rich sources of information for the rational design of anti-tubercular drugs, aiming to exploit unique and novel protein features and interactions based on atomic resolution structures. This review compiles structures of M. tuberculosis proteins elucidated since January 2007 that are promising avenues for drug design, encompassing proteins involved with known and experimental antituberculosis drugs, metabolism, dealing with the hostile environment of the host organism, and information processing.

Vascularized bone graft from the index metacarpal for Kienböck's disease: a case report.

A vascularized bone graft from the head and neck of the index metacarpal bone was used for the treatment of stage IIIA Kienböck's disease in a 20-year-old woman. Three months after surgery pain had disappeared and wrist range of motion improved. Postoperative radiographs and magnetic resonance imaging revealed revascularization and fracture healing of the lunate bone. This technique has not been used in the treatment of Kienböck's disease; it may be useful in selected cases.

Crystal structure of 3-amino-5-hydroxybenzoic acid (AHBA) synthase.

The biosynthesis of ansamycin antibiotics, including rifamycin B, involves the synthesis of an aromatic precursor, 3-amino-5-hydroxybenzoic acid (AHBA), which serves as starter for the assembly of the antibiotics' polyketide backbone. The terminal enzyme of AHBA formation, AHBA synthase, is a dimeric, pyridoxal 5'-phosphate (PLP) dependent enzyme with pronounced sequence homology to a number of PLP enzymes involved in the biosynthesis of antibiotic sugar moieties. The structure of AHBA synthase from Amycolatopsis mediterranei has been determined to 2.0 A resolution, with bound cofactor, PLP, and in a complex with PLP and an inhibitor (gabaculine). The overall fold of AHBA synthase is similar to that of the aspartate aminotransferase family of PLP-dependent enzymes, with a large domain containing a seven-stranded beta-sheet surrounded by alpha-helices and a smaller domain consisting of a four-stranded antiparallel beta-sheet and four alpha-helices. The uninhibited form of the enzyme shows the cofactor covalently linked to Lys188 in an internal aldimine linkage. On binding the inhibitor, gabaculine, the internal aldimine linkage is broken, and a covalent bond is observed between the cofactor and inhibitor. The active site is composed of residues from two subunits of AHBA synthase, indicating that AHBA synthase is active as a dimer.

Vascularized bone graft from the second metacarpal to the thumb: a case report.

Bony pedicled grafts arising from the second metacarpal have been described, mainly for the treatment of recurrent pseudarthrosis of the scaphoid. The clinical use of this graft has been extended for the management of nonunion of the proximal phalanx of the thumb.

Epidermotropic metastatic melanoma. Are the current histologic criteria adequate to differentiate primary from metastatic melanoma?

A case is reported of a patient with a lentiginous acral melanoma of the heel that was excised and recurred 3 years later at the margin of the previous scar. After another 3 years, a group of five small lesions appeared in the thigh that were considered to be junctional and epidermotropic metastases. The authors question the current histologic criteria for differentiating junctional and epidermotropic metastases of previous melanomas from multiple primary melanomas. It is concluded that the clinical history is of primary importance in reaching a correct diagnosis; histologic studies are not sufficient.

[Early gastric and superficial muscle gastric cancer. Contribution of morphology to prognosis]. / Cáncer gástrico precoz y muscular superficial. Aportación de la morfología al pronóstico.

The purpose of the study was to correlate the depth of invasion in the gastric wall with survival in gastric cancer. In order to do so, we reviewed 48 patients harboring 58 gastric adenocarcinomas that did not exceed the superficial half of the muscularis propia. The patients were followed for up to a period of a least 5 years after surgery. The depth of invasion of the tumour in the gastric wall was found to correlate significantly with the invasion of lymphatic capillaries (p < 0.001) and with the finding of lymph node metastasis (mucous cancer 9%, submucous cancer 36% and superficial muscularis propia cancer 40%; p < 0.05). The size of the tumour was directly related with the depth of the cancerous invasion. Survival after 5 years varies significantly according to size of tumour (< 2 cm = 100%, 2-5 cm = 86% and > 5 cm = 33%; p < 0.0001), invasion of lymphatic capillaries (p < 0.01) and depth of the cancerous invasion (mucous cancer 94%, submucous cancer 84% and superficial muscularis propia cancer 67%; p < 0.05). The Lauren diffuse type or the multicentric cancer had a worse prognosis. The depth of invasion in the gastric wall appears to be the most important prognostic factor, since both the size of the tumor and the lymphatic involvement are related to it. When the tumour is limited to the muscularis propia, the survival rate is intermediate between early gastric cancer and advanced cancer.

[Effects of met-enkephalin on the testis. II. Histochemical study]. / Efectos de la met-encefalina sobre el testículo. II. Estudio histoquímico.

We performed a histochemical study using the Alcian blue-PAS staining method (for mucopolysaccharide), vitamin C, Sudan black (for lipids), and methyl green-pyronine (for nucleic acid). For the study, we utilized 105 male Wistar rats weighing 280-300 gms. Thirty rats comprised the control group, and 75 comprised the study group. Rats in the study group received a single, acute intracardiac dose of met-enkephalin (100 microliters of 50% met-enkephalin solution) and were sacrificed at 15, 30 and 60 minutes following injection, or a chronic intramuscular dose (50 microliters of 40% met-enkephalin solution). We observed that met-enkephalin caused histochemical changes in the rat testis, as evidenced by the accumulation of mucopolysaccharide (early in the study), cytoplasm lipid degeneration, changes in protein synthesis, and a fall in vitamin C stores (in seminal epithelium cell lines, as well as Leydig cells). These changes were more marked in the chronically than in the acutely-treated rats. The foregoing findings demonstrate that enkephalins (endogenous opiates) can cause profound metabolic changes in the rat testis that affect all its metabolic elements [proteins, lipids, polysaccharides and active substances (vitamins...)].