Oncogenic and drug-sensitive NTRK1 rearrangements in lung cancer.

We identified new gene fusions in patients with lung cancer harboring the kinase domain of the NTRK1 gene that encodes the high-affinity nerve growth factor receptor (TRKA protein). Both the MPRIP-NTRK1 and CD74-NTRK1 fusions lead to constitutive TRKA kinase activity and are oncogenic. Treatment of cells expressing NTRK1 fusions with inhibitors of TRKA kinase activity inhibited autophosphorylation of TRKA and cell growth. Tumor samples from 3 of 91 patients with lung cancer (3.3%) without known oncogenic alterations assayed by next-generation sequencing or fluorescence in situ hybridization demonstrated evidence of NTRK1 gene fusions.

Increased prescribing trends of paediatric psychotropic medications.

Psychotropic medication use by children in the USA has increased. We used the IMS MIDAS Prescribing Insights to examine prescribing trends in nine countries between the years 2000 and 2002. Trends in seven countries rose significantly from year 2000 to 2002; the UK had the highest increase (68%).

Crystal structure determination of thymoquinone by high-resolution X-ray powder diffraction.

The crystal structure of 2-isopropyl-5-methyl-1,4-benzoquinone (thymoquinone) and its thermal behavior--as necessary physical and chemical properties--were determined in order to enhance the current understanding of thymoquinone chemical action by using high resolution x-ray powder diffraction, Fourier transform infrared spectroscopy (FTIR), and 3 thermo-analytical techniques thermogravimetric analysis (TGA), differential thermal analysis (DTA), and differential scanning calorimetry (DSC). The findings obtained with high-resolution x-ray powder diffraction and molecular location methods based on a simulated annealing algorithm after Rietveld refinement showed that the triclinic unit cell was a = 6.73728(8) A, b = 6.91560(8) A, c = 10.4988(2) A, alpha = 88.864(2) degrees, beta = 82.449(1) degrees, gamma = 77.0299(9) degrees; cell volume = 472.52(1) A3, Z = 2, and space group P1. In addition, FTIR spectrum revealed absorption bands corresponding to the carbonyl and C-H stretching of aliphatic and vinylic groups characteristically observed in such p-benzoquinones. Also, a chemical decomposition process starting at 65 degrees C and ending at 213 degrees C was noted when TGA was used. DSC allowed for the determination of onset at 43.55 degrees C and a melting enthalpy value of DeltaH(m) = 110.6 J/g. The low value obtained for the fusion point displayed a van der Waals pattern for molecular binding, and the thermograms performed evidence that thymoquinone can only be found in crystalline triclinic form, as determined by DRX methods.

Ultrastructural study on experimental infection of rotavirus in a murine heterologous model.

Viral replication, histopathological and ultrastructural changes were observed for a period of nine days in the small intestine of suckling mice infected with a simian rotavirus (SA11). Samples taken from duodenum, jejunum and ileum were prepared for light microscopy, transmission and scanning electron microscopy analysis. Histopathologic effect could be detected within 8 hr post-infection, when only a few altered cells were observed. Damage was extensive after 16 hr post-infection, showing swollen enterocytes and reduced and irregularly oriented microvilli at intestinal villi tips. Virus particles were detected at 16 and 48 hr post-infection, budding from the viroplasm into the rough endoplasmic reticulum cisternae in ileum enterocytes. Clear evidence of viral replication, observed by electron microscopy was not described before in heterologous murine models. Regeneration of the intestinal villi began at the third day post-infection. Despite some differences observed in clinical symptoms and microscopic analysis of homologous and heterologous rotavirus infections, we concluded that mechanisms of heterologous rotavirus infection in mice follow similar patterns to those observed in the homologous models.

Murine experimental infection with rotavirus SA-11: clinical and immunohistological characteristics.

Six- to eight-day old (lactent) mice were inoculated orally with simian SA-11 rotavirus. During the first hours after infection, the virus was already detected in villous apical enterocytes by immunohistologic reaction of paraffin sections of the duodenum and jejunum but not in the ileum. Late on the first day, some animals developed already diarrhoea and pathologic lesions were observed in the duodenum and jejunum. During the second day most mice developed diarrhoea; tissue lesions were intense and maximal from duodenum to ileum when compared to other days and some colon sections had mild pathological characteristics. At this point, the virus in the ileum was only detected by immunohistologic reaction. During the third day some animals still had diarrhoea but tissue histology was regenerated and no virus could be detected. We conclude that the SA-11 model follows an infection pattern similar to Epizootic Diarrhoea of Infant Mice (EDIM) and propose to study immunological parameters as young susceptible animals mature into adult resistant ones.