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John Armstrong

Publications and source records attributed to John Armstrong.

10 recordsLinked to original sources
PubMed2006

African swine fever virus causes microtubule-dependent dispersal of the trans-golgi network and slows delivery of membrane protein to the plasma membrane.

Viral interference with secretory cargo is a common mechanism for pathogen immune evasion. Selective down regulation of critical immune system molecules such as major histocompatibility complex (MHC) proteins enables pathogens to mask themselves from their host. African swine fever virus (ASFV) disrupts the trans-Golgi network (TGN) by altering the localization of TGN46, an organelle marker for the distal secretory pathway. Reorganization of membrane transport components may provide a mechanism whereby ASFV can disrupt the correct secretion and/or cell surface expression of host proteins. In the study reported here, we used the tsO45 temperature-sensitive mutant of the G protein of vesicular stomatitis virus to show that ASFV significantly reduces the rate at which the protein is delivered to the plasma membrane. This is linked to a general reorganization of the secretory pathway during infection and a specific, microtubule-dependent disruption of structural components of the TGN. Golgin p230 and TGN46 are separated into distinct vesicles, whereupon TGN46 is depleted. These data suggest that disruption of the TGN by ASFV can slow membrane traffic during viral infection. This may be functionally important because infection of macrophages with virulent isolates of ASFV increased the expression of MHC class I genes, but there was no parallel increase in MHC class I molecule delivery to the plasma membrane.

African Swine Fever Virus↗
PubMed2005

Hyphal Growth in the Fission Yeast Schizosaccharomyces pombe.

The fission yeast Schizosaccharomyces pombe grows in a single-celled form or can mate and undergo meiosis and sporulation. Here we show that wild-type S. pombe can also differentiate to form elaborately branched hyphae which invade deep into solid medium. Branches appear in the hyphae adjacent to unseparated septa. Electron microscopy reveals unusual multivesicular structures within the hyphae. Nitrogen deprivation appears to be the main stimulus for hyphal growth. No mitogen-activated protein kinase is necessary for the response. Inhibition of cyclic AMP (cAMP) production or signaling prevents the response, and exogenous cAMP promotes it, suggesting that detection of a good carbon source is required for hyphal growth but not for mating.

Cell Proliferation↗
PubMed2004

IntAct: an open source molecular interaction database.

IntAct provides an open source database and toolkit for the storage, presentation and analysis of protein interactions. The web interface provides both textual and graphical representations of protein interactions, and allows exploring interaction networks in the context of the GO annotations of the interacting proteins. A web service allows direct computational access to retrieve interaction networks in XML format. IntAct currently contains approximately 2200 binary and complex interactions imported from the literature and curated in collaboration with the Swiss-Prot team, making intensive use of controlled vocabularies to ensure data consistency. All IntAct software, data and controlled vocabularies are available at http://www.ebi.ac.uk/intact.

Animals↗
PubMed2004

Escalated dose for non-small-cell lung cancer with accelerated hypofractionated three-dimensional conformal radiation therapy.

BACKGROUND AND PURPOSE: To prospectively assess the feasibility and efficacy of a hypofractionated accelerated radiotherapy regimen (72 Gy in 24 daily fractions, 3 Gy per fraction) in patients (pts) with non-resectable non-small-cell lung cancer (NSCLC). MATERIAL AND METHODS: We included 25 pts with a histologically or cytologically proven NSCLC, with KPS > or = 70 and < or =10% weight loss over prior three months, and with tumour stage I/II medically inoperable (9 pts) or non-resectable stage III a/b without pleural effusion (16 pts). Eleven pts received induction chemotherapy. No more than 30% of the combined lung volume could receive more than 25 Gy and the maximal biological effective dose to the spinal cord was maintained below 44 Gy. RESULTS: No grade-4 acute toxicity event was reported. Two pts had a treatment break because of grade-3 acute oesophagitis. Twenty-two pts were evaluable for long-term toxicity (median follow-up=9.7 months, range 4 to 30.2 months). There were 4 Grade-1 pulmonary and 2 Grade-1 oesophageal long-term toxicity events. Twenty-two pts were evaluable for tumour response with 7 complete and 8 partial responses, 5 stable diseases and 2 progressive diseases. The actuarial 1-year overall and thoracic-progression-free survival rates were 68% and 72% respectively. CONCLUSIONS: This study demonstrates the feasibility of the experimental radiotherapy schedule, however more data are needed to confirm its efficacy.

Aged↗
PubMed2004

Profile and outcome of pure androgen-secreting adrenal tumors in women: experience of 21 cases.

BACKGROUND: The aim of the study was to determine the outcome and possible prognostic factors of pure androgen-secreting adrenal tumors (PASATs). METHODS: In a review of 801 adrenal operations from 1970 through 2003, 21 women with PASATs were divided into 2 groups, benign and undetermined tumors (Weiss score < or = 3) (BT = 11) and malignant tumors (Weiss > or =4 or nonresectable) (MT = 10). RESULTS: In both groups, age at presentation was similar. There were no differences concerning type of secretion, but increase in testosterone level was 2.6-fold greater in malignant tumors (MT) than benign tumors (BT). Imaging studies allowed diagnosis of malignancy in 4 of 10 MT. Size and weight were greater for MT than for BT (average, 13.7 vs 9.2 cm and 1462 vs 206 g). At follow-up (median, 17 y; range, 1 to 33 y) 2 of 11 patients with BT died of unrelated causes, and 9 of 11 are alive without recurrence; 5 of 10 patients with MT died of disease, and 3 are alive with disease; 7 of those 8 patients had stage III or IV disease and/or had a Weiss score of 6 or greater. Two patients with MT are alive without disease; both were Weiss 7, stage II and received mitotane postoperatively. CONCLUSIONS: PASATs of undetermined benign condition share the good prognosis of BT. Weiss score is diagnostic of malignancy. MacFarlane classification determines the prognosis, and long-term disease-free survivors at stages III/IV are never observed after operation only. Postoperative mitotane therapy might be beneficial at stage II.

Adolescent↗
PubMed2003

Analysis of dose distribution in the 'Rind'--a volume outside the PTV--in 3-dimensional conformal radiation therapy of non-small cell lung cancer.

BACKGROUND AND PURPOSE: Appropriate planning target volume (PTV) definition is critical for local disease eradication in the treatment of non-small cell lung cancer (NSCLC). When margins are added to the gross tumour volume (GTV) in the standard way, the PTV formed may be too large to facilitate dose escalation due to normal tissue tolerance. To increase the feasibility of dose escalation with 3-dimensional conformal radiotherapy (3DCRT), this study examines an alternative method for the formation of the PTV in NSCLC. This strategy is based on the reduced probability of tumour cells from the GTV outwards and on the associated lower dose requirements to eradicate such subclinical disease. MATERIALS AND METHODS: 3DCRT plans were generated from the CT scans of 15 patients with NSCLC (stages Ib to IIIb). Each PTV was formed by adding a margin for geometric uncertainties directly onto the GTV. The success of this approach is dependent on the volume immediately outside this smaller PTV, the Rind volume, receiving 50 Gy, the minimum dose requirement that is considered sufficient for eradication of the reduced tumour cell density in this volume. While optimizing the treatment plans for each PTV to 70 Gy, the dose distribution in the Rind volume, and the factors affecting it, were assessed. RESULTS: One hundred percent of each PTV received a minimum of 95% of the prescribed dose. The percentage of the Rind volume receiving 50 Gy or more (V50) had a median value of 94%. The minimum dose in this volume, however, ranged from 5.6 to 32.1 Gy. The V50 was highest for apical tumours (96.1%) and lowest for peripheral tumours (86%) and correlated positively with the size of the PTV (Kendall's rank correlation (Kt)=+0.3, P=0.05) and the number of beams used (Kt=+0.3, P=0.03) but not with the conformity index. The average volume outside the Rind which still received >/=50 Gy (the Wasted 50 Gy) increased significantly with the V50 of the Rind volume and was inversely proportional to the Rind <50 Gy, correlating significantly with the dose to the organs at risk. CONCLUSIONS: Using this strategy with standard 3DCRT, all PTVs were irradiated to the required dose with this approach, but none of the corresponding Rind volumes had an acceptable dose distribution. The addition of dual volume planning or the use of intensity modulated radiation therapy may achieve an appropriate dose distribution in the Rind volume while not increasing the dose to the organs at risk and may thereby facilitate dose escalation.

Aged↗