Antibiotic hyper-resistance in a class I aminoacyl-tRNA synthetase with altered active site signature motif.

Antibiotics target key biological processes that include protein synthesis. Bacteria respond by developing resistance, which increases rapidly due to antibiotics overuse. Mupirocin, a clinically used natural antibiotic, inhibits isoleucyl-tRNA synthetase (IleRS), an enzyme that links isoleucine to its tRNAIle for protein synthesis. Two IleRSs, mupirocin-sensitive IleRS1 and resistant IleRS2, coexist in bacteria. The latter may also be found in resistant Staphylococcus aureus clinical isolates. Here, we describe the structural basis of mupirocin resistance and unravel a mechanism of hyper-resistance evolved by some IleRS2 proteins. We surprisingly find that an up to 103-fold increase in resistance originates from alteration of the HIGH motif, a signature motif of the class I aminoacyl-tRNA synthetases to which IleRSs belong. The structural analysis demonstrates how an altered HIGH motif could be adopted in IleRS2 but not IleRS1, providing insight into an elegant mechanism for coevolution of the key catalytic motif and associated antibiotic resistance.

In vitro antiproliferative study of novel adamantyl pyridin-4-ones.

The preparation of several N-aryl-substituted (phenyl, p-methylphenyl, p-methoxyphenyl, p-nitrophenyl, p-aminophenyl, p-hydroxyphenyl) 3-hydroxy-2-methylpyridin-4-ones as well as their adamantyl derivatives is described, and their in vitro antitumor properties were investigated. The compounds were synthesized in good yields using efficient synthetic routes and methods. Prepared derivatives were evaluated in an antiproliferative in vitro study on 4 cancer cell lines, namely HCT 116 (colon carcinoma), H 460 (lung carcinoma), MCF-7 (breast carcinoma) and K562 (chronic myelogenous leukemia). All tested compounds showed antiproliferative activity ranging from moderate to strong on all inspected cell lines with 4 adamantane containing derivatives being active and selective at low micromolar IC[Formula: see text] concentrations on HCT 116, H 460 and MCF-7. LDH cytotoxicity assay revealed that cytotoxic effects occur after 48 h of exposure. It was shown that there was no change in caspase activity in the treated cells, but there were changes in the cell cycle. All treated samples showed reduced number of cells in the S phase with increased G0/G1 (4b, 5a, 5b) and G2/M (4a) phase.

Classic migraine and visual field defects.

A series of 116 patients with classic migraine were studied to record visual field defects. Thirty-four (29.3%) subjects had defects of the field of vision, 11 of them bilaterally, which made a total of 45 (19.4%) eyes. Downward isopter depression from above and contraction of the field of vision were the most common damages. A homonymous hemianopic defect was found in seven patients. The area of depressed vision helps to some extent in anatomical localization of the damage. Its etiology has not been fully clarified. The authors recommend more extensive clinical examinations of the visual field, i.e. follow-up of each patient with classic migraine by periodical testing of the field of vision.

[Bilateral glomus caroticum tumors]. / Bilateralni tumori karotickoga glomusa.

Paragangliomas of the head and neck are tumors which are believed to function as chemosensory reflex receptors that respond to changes in their chemical environment. They may occur in the carotid body, on the vagus nerve, along the jugular vein, in the middle ear, in the orbit, in the larynx and nasopharynx. The incidence of multiple paragangliomas is about 3% of all the patients with this tumor and 26% of the patients with positive family history.

Nasopharyngeal cancer and blood selenium level.

A case-control study of nasopharyngeal carcinoma was performed in Zagreb from 1989 until 1993. Blood selenium concentrations were determined in 34 patients with nasopharyngeal cancer and 47 normal subjects by means of the atomic absorption spectrophotometric method. The sera of nasopharyngeal cancer patients showed no significant differences in selenium values from the sera of normal individuals, but there were significant differences between patients with enlarged cancer (T4 stage) and normal individuals. The results suggest that lower blood selenium levels in this group of nasopharyngeal cancer patients may be a consequence of their disease, rather than the cause of the cancer.

[Auditory evoked potentials in alcoholics]. / Slusni evocirani potencijali kod alkoholicara.

In this paper, auditory brain stem potentials in the group of 26 alcoholics were studied and a significantly delayed latencies of the peaks II through V as compared to the healthy control subjects were found. In addition, a statistically significant prolongation of brain stem transmission time (BTT) in alcoholics was observed. The study also suggests the possibility of monitoring the level of pathohistological changes of the central auditory pathway caused by excessive alcohol consumption.

[Bronchogenic carcinoma of the lungs in 3 workers with asbestosis employed in the same factory]. / Bronhogeni karcinom pluca u tri radnika s azbestozom iz iste tvornice.

In two female workers (nonsmokers) and in one male worker (a smoker) employed in the same mill with a history of asbestosis, bronchogenic lung carcinoma type adenocarcinoma (women), respectively anaplastic carcinoma (a man) had developed. All the three patients worked in the same area in a spinning-mill. The duration of exposure to asbestos was relatively short (10 to 15 years) in female workers, while the duration of exposure to asbestos was much longer in a male worker (29 years), although it was intermittent. Dyspnea was the main and the only discomfort. In accordance with the International Labour Organization (ILO) classification, a chest radiograph revealed the lesions of s/t 1/2 and s/t 2/1 features. There was also a ventilation deficit (very decreased carbon monoxide diffusing capacity).

[Pulmonary alveolar microlithiasis]. / Plucna alveolarna mikrolitijaza.

Essential knowledge of pulmonary alveolar microlithiasis is displayed in connection with the instructive case report that points out how important is to bear in mind also such a rare pulmonary disease in a diagnostic procedure.