Epstein–Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) up-regulates the human leukocyte antigen (HLA) class I antigen presentation machinery (APM). This appears counterintuitive with immune evasion in EBV-associated tumours like nasopharyngeal carcinoma (NPC).
Latent membrane protein 1-transfected epithelial cell lines were used as a model system to study the impact of LMP1 and c-Myc on HLA class I components. The expression of components of the HLA class I APM, c-Myc and Ki-67 was analysed in LMP1+ and LMP1− NPC by immunohistochemistry.
In epithelial cells, LMP1 up-regulated HLA class I APM. This effect could be counteracted by c-Myc, which itself was up-regulated by LMP1 apparently through IL6 induction and Jak3/STAT3 activation. Studies of NPC biopsies revealed down-regulation of HLA class I APM expression. No difference was observed between LMP1+ and LMP1− NPC. However, expression of Ki-67 and c-Myc were up-regulated in LMP1+ tumours.
These findings raise the possibility that c-Myc activation in NPC might antagonise the effect of LMP1 on HLA class I expression thus contributing to immune escape of tumour cells.
HLA class I; LMP1; EBV; NPC
Temporomandibular joint dislocation is not a common presentation to the emergency department but it is one that requires prompt diagnosis and reduction. This is thought to be the first reported case of spontaneous bilateral temporomandibular joint dislocation after routine pulmonary function testing. The management of the case is discussed and a review of closed reduction techniques commonly used in the emergency department is presented.
A critical component of flagellar assembly, the kinesin-2 heterotrimeric complex powers the anterograde movement of proteinaceous rafts along the outer doublet of axonemes in intraflagellar transport (IFT). We present the first high-resolution structures of a kinesin-2 motor domain and an ATP hydrolysis–deficient motor domain mutant from the parasitic protist Giardia intestinalis. The high-resolution crystal structures of G. intestinalis wild-type kinesin-2 (GiKIN2a) motor domain, with its docked neck linker and the hydrolysis-deficient mutant GiKIN2aT104N were solved in a complex with ADP and Mg2+ at 1.6 and 1.8 Å resolutions, respectively. These high-resolution structures provide unique insight into the nucleotide coordination within the active site. G. intestinalis has eight flagella, and we demonstrate that both kinesin-2 homologues and IFT proteins localize to both cytoplasmic and membrane-bound regions of axonemes, with foci at cell body exit points and the distal flagellar tips. We demonstrate that the T104N mutation causes GiKIN2a to act as a rigor mutant in vitro. Overexpression of GiKIN2aT104N results in significant inhibition of flagellar assembly in the caudal, ventral, and posterolateral flagellar pairs. Thus we confirm the conserved evolutionary structure and functional role of kinesin-2 as the anterograde IFT motor in G. intestinalis.
Much evidence now attests to the importance of desmosomes and their constituents in cancer. Alterations in the expression of desmosomal components could contribute to the progression of the disease by modifying intracellular signal transduction pathways and/or by causing reduced cell adhesion. The Wnt/β-catenin pathway is a potential target because of the involvement of the cytoplasmic desmosomal protein plakoglobin. Loss of desmosomal adhesion is a prerequisite for the epithelial–mesenchymal transition, implicated in the conversion of early stage tumours to invasive cancers.
desmosome; desmocollin; desmoglein; plakoglobin; EMT
Naturally acquired infection of humans with a marine mammal-associated Brucella sp. has only been reported once previously in a study describing infections of two patients from Peru. We report the isolation and characterization of a strain of Brucella from a New Zealand patient that appears most closely related to strains previously identified from marine mammals. The isolate was preliminarily identified as Brucella suis using conventional bacteriological tests in our laboratory. However, the results profile was not an exact match, and the isolate was forwarded to four international reference laboratories for further identification. The reference laboratories identified the isolate as either B. suis or B. melitensis by traditional bacteriological methods in three laboratories and by a molecular test in the fourth laboratory. Molecular characterization by PCR, PCR-restriction fragment length polymorphism, and DNA sequencing of the bp26 gene; IS711; the omp genes omp25, omp31, omp2a, and omp2b; IRS-PCR fragments I, III, and IV; and five housekeeping gene fragments was conducted to resolve the discrepant identification of the isolate. The isolate was identified to be closely related to a Brucella sp. originating from a United States bottlenose dolphin (Tursiops truncatus) and common seals (Phoca vitulina).
Giardia lamblia cell populations show 90% detachment from glass under normal forces of 2.43 ± 0.33 nN applied by centrifugation. Detachment forces were not significantly different for cells attached to positively charged, hydrophobic, or inert surfaces than for cells attached to plain glass. The insensitivity of attachment force to surface treatment is consistent with a suction-based mechanism of attachment.
Ankle arthroplasty for post-traumatic tibiotalar arthritis remains controversial. The current literature strongly recommends arthrodesis, especially in those patients who will overload the joint: the young, the active and the overweight patients. The case described here is a 40-year follow up. A 31-year old man underwent talar dome resurfacing with a custom Vitallium implant for post-traumatic arthritis in 1962. He continued to work as a heavy laborer until retirement in 1987 and presently remains virtually asymptomatic with regard to his foot and ankle.
The longevity of this individual implant has been remarkable. The unique design, minimal resection, surgical approach and remarkable success merit discussion in the light of publication of predominantly bleak reports of arthroplasty in this patient population.
Solar evaporation ponds are commonly used to reduce the volume of seleniferous agricultural drainage water in the San Joaquin Valley, Calif. These hypersaline ponds pose an environmental health hazard because they are heavily contaminated with selenium (Se), mainly in the form of selenate. Se in the ponds may be removed by microbial Se volatilization, a bioremediation process whereby toxic, bioavailable selenate is converted to relatively nontoxic dimethylselenide gas. In order to identify microbes that may be used for Se bioremediation, a 16S ribosomal DNA phylogenetic analysis of an aerobic hypersaline pond in the San Joaquin Valley showed that a previously unaffiliated group of uncultured bacteria (belonging to the order Cytophagales) was dominant, followed by a group of cultured γ-Proteobacteria which was closely related to Halomonas species. Se K-edge X-ray absorption spectroscopy of selenate-treated bacterial isolates showed that they accumulated a mixture of predominantly selenate and a selenomethionine-like species, consistent with the idea that selenate was assimilated via the S assimilation pathway. One of these bacterial isolates (Halomonas-like strain MPD-51) was the best candidate for the bioremediation of hypersaline evaporation ponds contaminated with high Se concentrations because it tolerated 2 M selenate and 32.5% NaCl, grew rapidly in media containing selenate, and accumulated and volatilized Se at high rates (1.65 μg of Se g of protein−1 h−1), compared to other cultured bacterial isolates.
AIM—To determine whether existing information and surveillance systems can be used to provide follow up data on groups of infants at increased risk of disability—for example, the survivors of neonatal intensive care.
METHODS—A survey was made of maternity, neonatal, and community child health information systems and surveillance programmes in the Trent Regional Health Authority. Children known to have received neonatal intensive care in Trent between 1 August 1992 and 31 July 1993, and a random sample of normal children in two health districts (data quality check) were included. A data linkage study was made to determine whether follow up information about a random sample of infants, known to be at increased risk of poor outcome, could be identified on community child health databases. Two widely accepted datasets (birth and 2 years) were used as standards for this exercise. The quality of data was audited.
RESULTS—All clinical items of the birth minimum dataset were routinely recorded by at least one agency in each health district in Trent. Of the descriptive items, only the mother's age on leaving full time education was not collected. At 2 years, all clinical items were collected as part of the routine surveillance programme, but data were recorded using a system which severely limited interpretation. Data quality, in terms of the number of errors introduced at data entry, was very good with only 1.1% of the check items (4/368) incorrectly recorded. Only two districts had organised electronic transfer of data between maternity, neonatal, and community child health systems. The mother's NHS number, although available, was not routinely recorded by any system. The NHS number of the infant was routinely collected by six out of 12 community paediatric services. Data linkage was attempted in six districts with appropriate community child health databases. Just over 70% of the intensive care sample was successfully linked with follow up information on child health systems.
CONCLUSIONS—The existing programmes for routine child surveillance could provide outcome data for high risk groups of infants, such as the survivors of neonatal intensive care. However, the present coding system used for data entry is inadequate. Furthermore, rates of identification, without the use of a unique identifier (NHS number) for each subject, are currently insufficient for monitoring health status in later life.
Keywords: outcome data; information systems; surveillance programmes; intensive care
The association of Epstein-Barr virus (EBV) with various malignancies is well established but the pattern of EBV latent gene expression in these different tumours is variable, reflecting distinct aspects of the virus–cell interaction. These different forms of EBV latency are associated with phenotypic variation and highlight the influence of EBV latent proteins on cell growth and survival. The EBV latent proteins have distinct functions associated with the maintenance of EBV infection and the control of various signalling and transcriptional pathways that facilitate the proliferation and survival of infected cells. Understanding the function of these EBV latent proteins will not only provide insight into the mechanisms governing fundamental cell processes but will also identify targets for novel treatment.
Epstein-Barr virus; EBV latent genes
The effect of amending soil held at 3 different moisture levels with glucose, unsulfured molasses, or nutrient broth (0.3, 0.7, 3.2, 7.1 g carbon/100 g) on Tylenchorhynchus claytoni and T. dubius was investigated. When soil was held under saturated or flooded conditions in the absence of carbon amendments for 7 days, Tylenchorhynchus populations were 19% and 16%, respectively, of the controls. Carbon amendments at all levels tested precipitated a further decline in the nematode population to 1% or less of the unamended controls in 7 days. Two applications of molasses (7.4%, w/w) 3 days apart to nematode-infested soil held in Conetainers under mist for 7 days reduced Tylenchorhynchus spp. and Hoplolaimus galeatus densities to 7% and 3%, respectively, of the controls. Nematode densities in turfgrass field plots also declined following irrigation and repeated drenching with a molasses solution. Based on the observed decline in redox potential and pH in saturated soil, especially following carbon amendment, we propose that the activity of anaerobic fermentative bacteria was responsible for the reduction in nematode densities.
carbon; Hoplolaimus galeatus; moisture; molasses; nematode; pH; redox; Tylenchorhynchus claytoni; Tylenchorhynchus dubius
Three high-pressure liquid injection machines were used to inject isazofos into the root zone of tuff`grass plots to evaluate its potential for control of Hoplolaimus galeatus and Tylenchorhynchus dubius. A Rogers root zone injector delivering isazofos at 2.3 kg a.i./ha through 30° and 60° spray tips at 5,000 psi (3.45 × 10⁷ Pascals) significantly reduced nematode populations at 32 days after a single application and 33 days after a second application. In a second experiment with the Rogers injector at 2.3 kg a.i./ha, H. galeatus populations were significantly lower at 16 days after a single application and at 42 and 61 days after a second application with the 60° spray angle tips. An Envirojet turfgrass injector used to inject isazofos at 1.15 kg a.i./ha and 2.88 kg a.i./ha at 3,000 psi (1.38 × 107 Pascals) significantly reduced nematode populations at 7 days after treatment at the low rate and at 63 days after treatment with both application rates. A Landpride material injector applying isazofos at 6.9 and 13.8 kg a.i./ha at 2,000 psi (1.38 × 10⁷ Pascals) significantly reduced nematode populations at 7, 14, and 63 days after treatment at the high rate and at 63 days after the low-rate application. Although suppression of nematodes with isazofos was found, the degree of suppression is probably not enough to warrant recommendation of high-pressure delivery of isazofos for control of H. galeatus and T. dubius populations infesting turfgrasses.
Agrostis canina; Agrostis palustris; annual bluegrass; control; creeping bentgrass; high-pressure liquid injection; Hoplolaimus galeatus; isazofos; Lolium perenne; nematicide; nematode; perennial ryegrass; Poa annua; tuff`grass; Tylenchorhynchus dubius; velvet bentgrass
A fluorescent pseudomonad (strain CW-96-1) isolated from a deep-sea vent sample grew at 30 degrees C under aerobic conditions in an artificial seawater medium and tolerated cadmium concentrations up to 5 mM. After 140 h, strain CW-96-1 removed > 99% of the cadmium from solution. Energy dispersive microanalysis revealed that the cadmium was removed by precipitation on the cell wall; sulfide production was confirmed by growth on Kligler's agar. Based on 16S ribosomal DNA sequencing and fatty acid analysis, the microorganism is closely related to Pseudomonas aeruginosa.
AIMS: Possible risk factors were evaluated for herpes simplex virus (HSV) epithelial keratitis in patients with stromal keratouveitis. METHODS: The study population included 260 patients who had active stromal keratitis and/or iridocyclitis without epithelial disease and who were enrolled in one of three clinical trials of the Herpetic Eye Disease Study. Study treatment involved a 10 week course of topical placebo, topical prednisolone phosphate, or topical prednisolone phosphate with oral acyclovir. All groups received topical trifluridine four times daily for 3 weeks then twice daily for another 7 weeks. Patients were examined for HSV epithelial keratitis for 16 weeks. RESULTS: Dendritic or geographic epithelial keratitis occurred in 12 (4.6%) study patients. Adverse effects attributable to trifluridine prophylaxis were acute allergic blepharoconjunctivitis in 10 (3.8%) study patients and corneal epithelial erosions in 11 (4.2%) study patients. No significant difference in the occurrence of HSV epithelial keratitis was found among the study treatment groups: one (2.0%) of 49 topical placebo treated patients, nine (6.5%) of 138 patients treated with topical corticosteroids without acyclovir, and two (2.7%) of 73 patients treated with topical corticosteroids and oral acyclovir. Univariate exponential models suggested that patients with a history of previous HSV epithelial keratitis and non-white patients were more likely to develop HSV epithelial keratitis during treatment of stromal keratouveitis. CONCLUSION: Individuals with prior HSV epithelial keratitis and certain ethnic groups may have a higher rate of recurrent epithelial keratitis during the acute treatment of HSV stromal keratouveitis.