Decreased expression of eukaryotic initiation factor 3f deregulates translation and apoptosis in tumor cells.

The eukaryotic initiation factor 3f (eIF3f) is the p47 subunit of the multi-subunit eIF3 complex. eIF3 plays an important role in translation initiation. In the present study, we investigate the biological function of eIF3f in translation and apoptosis in tumor cells. We demonstrated for the first time that eIF3f is downregulated in most human tumors using a cancer profiling array and confirmed by real-time reverse transcription PCR in melanoma and pancreatic cancer. Overexpression of eIF3f inhibits cell proliferation and induces apoptosis in melanoma and pancreatic cancer cells. Silencing of eIF3f protects melanoma cells from apoptosis. We further investigated the biological function of eIF3f. In vitro translation studies indicate that eIF3f is a negative regulator of translation and that the region between amino acids 170 and 248 of eIF3f is required for its translation regulatory function. Ectopic expression of eIF3f inhibits translation and overall cellular protein synthesis. Ribosome profile and ribosomal RNA (rRNA) fragmentation assays revealed that eIF3f reduces ribosomes, which may be associated with rRNA degradation. We propose that eIF3f may play a role in ribosome degradation during apoptosis. These data provide critical insights into the cellular function of eIF3f and in linking translation initiation and apoptosis.

Biotransformation of irbesartan in man.

The metabolism of irbesartan, a highly selective and potent nonpeptide angiotensin II receptor antagonist, has been investigated in humans. An aliquot of pooled urine from healthy subjects given a 50-mg oral dose of [14C]irbesartan was added as a tracer to urine from healthy subjects that received multiple, 900-mg nonradiolabeled doses of irbesartan. Urinary metabolites were isolated, and structures were elucidated by mass spectroscopy, proton NMR, and high-performance liquid chromatography (HPLC) retention times. Irbesartan and the following eight metabolites were identified in human urine: (1) a tetrazole N2-beta-glucuronide conjugate of irbesartan, (2) a monohydroxylated metabolite resulting from omega-1 oxidation of the butyl side chain, (3, 4) two different monohydroxylated metabolites resulting from oxidation of the spirocyclopentane ring, (5) a diol resulting from omega-1 oxidation of the butyl side chain and oxidation of the spirocyclopentane ring, (6) a keto metabolite resulting from further oxidation of the omega-1 monohydroxy metabolite, (7) a keto-alcohol resulting from further oxidation of the omega-1 hydroxyl of the diol, and (8) a carboxylic acid metabolite resulting from oxidation of the terminal methyl group of the butyl side chain. Biotransformation profiles of pooled urine, feces, and plasma samples from healthy male volunteers given doses of [14C]irbesartan were determined by HPLC. The predominant drug-related component in plasma was irbesartan (76-88% of the plasma radioactivity). None of the metabolites exceeded 9% of the plasma radioactivity. Radioactivity in urine accounted for about 20% of the radiolabeled dose. In urine, irbesartan and its glucuronide each accounted for about 5 to 10% of the urinary radioactivity. The predominant metabolite in urine was the omega-1 hydroxylated metabolite, which constituted about 25% of the urinary radioactivity. In feces, irbesartan was the predominant drug-related component (about 30% of the radioactivity), and the primary metabolites were monohydroxylated metabolites and the carboxylic acid metabolite. Irbesartan and these identified metabolites constituted 90% of the recovered urinary and fecal radioactivity from human subjects given oral doses of [14C]irbesartan.

Dactylocyclines, novel tetracycline derivatives produced by a Dactylosporangium sp. II. Structure elucidation.

Fermentation of Dactylosporangium sp. (ATCC 53693) produces a mixture of tetracycline derivatives from which several related tetracycline glycosides, the dactylocyclines, were isolated and their structures determined. The most abundant glycoside in initial fermentations was found to be dactylocycline A. Each glycoside proved to be acid sensitive and readily hydrolyzed to a common aglycone, dactylocyclinone. While the aglycone was cross resistant with tetracycline, the dactylocyclines proved active against certain tetracycline-resistant organisms.

Lanomycin and glucolanomycin, antifungal agents produced by Pycnidiophora dispersa. II. Structure elucidation.

Two novel antifungal agents, lanomycin and glucolanomycin, as well as a biologically inactive degradation product, lanomycinol, were isolated from liquid fermentations of Pycnidiophora dispersa. All three compounds share an E,E,E-triene appended to a pyran ring. Lanomycin contains a glycine ester and glucolanomycin possesses a glucose unit attached to the glycine nitrogen. The structures, including absolute stereochemistry, were determined by spectroscopic analysis and partial chemical degradation. Both of the glycine containing compounds show activity against several pathogenic fungi in vitro.

Mineralogic information from a new airborne thermal infrared multispectral scanner.

A new six-channel aircraft multispectral scanner has been developed to exploit mineral signature information at wavelengths between 8 and 12 micrometers. Preliminary results show that igneous rock units can be identified from their free silica content, and that carbonate as well as clay-bearing units are readily separable on the digitally processed images.

Value of M-mode echocardiography for non-invasive diagnosis of Ebstein's anomaly.

M-mode echocardiographic studies were performed in 11 patients, most of them adults, with Ebstein's anomaly of the tricuspid valve, proven by cardiac catheterisation. Simultaneous recordings of the tricuspid and mitral valves were obtained in all cases, the transducer position being outside the left midclavicular line in seven patients. Tricuspid valve closure followed mitral valve closure in all cases, with an interval ranging between 0.04 and 0.14 s. Since, in more than 8500 routine echocardiographic studies a valve closure interval between 0.09 and 0.12 s was seen in only one patient without Ebstein's anomaly, an interval of 0.065 s or more should be regarded as diagnostic of Ebstein's disease; however, an interval shorter than 0.065 s does not exclude this diagnosis. In all patients a paradoxical septal movement was found. Two patients showed an atypical three-peaked diastolic pattern of movement of the anterior tricuspid leaflet and one patient also showed mitral valve prolapse. Pathological tricuspid valve closure delay, shown by echocardiography, makes it possible to diagnose Ebstein's anomaly in many cases without resort to cardiac catheterisation which has a relatively high risk in this disease.

Middle infrared multispectral aircraft scanner data: analysis for geological applications.

Multispectral middle IR (8-13-microm) data were acquired with an aircraft scanner over Utah. Because these digital image data were dominated by temperature, all six channels were highly correlated. Extensive processing was required to allow geologic photointerpretation based on subtle variations in spectral emittance between rock types. After preliminary processing, ratio images were produced and color ratio composites created from these. Sensor calibration and an atmospheric model allowed determination of surface brightness, temperature, emittance, and color composite emittance images. The best separation of major rock types was achieved with a principal component transformation, followed by a Gaussian stretch, followed by an inverse transformation to the original axes.