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1.  Epstein–Barr virus microRNAs and lung cancer 
British Journal of Cancer  2011;105(2):320-326.
Background:
We conducted the first analysis of viral microRNAs (miRNAs) in lung cancer, with a focus on Epstein–Barr virus (EBV).
Methods:
We evaluated viral miRs with a two-channel oligo-array targeting mature, anti-sense miRNAs in 290 cases. In 48 cases, we compared microarray and real-time quantitative PCR (qPCR) expression for three EBV miRNAs. We tested for EBV DNA, RNA, and protein in tumour tissue from six cases with and six cases without strong qPCR-based evidence of EBV miRNAs.
Results:
The EBV miRNAs strongly differentiated between adenocarcinoma and squamous cell carcinoma using the microarray (P<0.01 for 9 out of 16 EBV miRNAs). However, microarray and qPCR measurements of BART1, BART2, and BHRF1–3 expression were not significantly correlated (P=0.53, 0.94, and 0.47, respectively). Although qPCR provided substantial evidence of EBV miRNAs in 7 out of 48 cases, only 1 of these 7 cases had detectable EBV DNA in tumour tissue. None had detectable EBV RNA or protein by histochemical stains.
Conclusion:
In a comprehensive evaluation of EBV miRNA, DNA, RNA, and protein in lung cancer, we found little evidence of EBV in lung tumour tissue. Discrepancies between microarray- and qPCR-based strategies highlight the difficulty of validating molecular markers of disease. Our results do not support a role of EBV in lung cancer.
doi:10.1038/bjc.2011.221
PMCID: PMC3142804  PMID: 21654679
Epstein–Barr virus; lung cancer; microRNA; microarray; qPCR
2.  Overview of the Oral HIV/AIDS Research Alliance Program 
Advances in Dental Research  2011;23(1):28-33.
The Oral HIV/AIDS Research Alliance is part of the AIDS Clinical Trials Group, the largest HIV clinical trial organization in the world, and it is funded by the National Institute of Dental and Craniofacial Research, in collaboration with the National Institute of Allergy and Infectious Diseases. The alliance’s main objective is to investigate the oral complications associated with HIV/AIDS as the epidemic is evolving—in particular, the effects of potent antiretrovirals on the development of oral mucosal lesions and associated fungal and viral pathogens. Furthermore, oral fluids are being explored for their potential monitoring and diagnostic role with respect to HIV disease and coinfections. This article presents an overview of the alliance, its scientific agenda, and an outline of the novel interventional and noninterventional clinical studies ongoing and developing within the AIDS Clinical Trials Group infrastructure in the United States and internationally.
doi:10.1177/0022034511399084
PMCID: PMC3144044  PMID: 21441477
HIV/AIDS; OHARA; infectious diseases; AIDS Clinical Trials Group; oral cavity
3.  Experimental Transmission of Kaposi's Sarcoma–Associated Herpesvirus (Kshv/Hhv-8) to Scid-Hu Thy/Liv Mice 
The Journal of Experimental Medicine  1999;190(12):1857-1868.
Kaposi's sarcoma–associated herpesvirus (KSHV/HHV-8) is a novel human lymphotropic herpesvirus linked to several human neoplasms. To date, no animal model for infection by this virus has been described. We have examined the susceptibility of C.B-17 scid/scid mice implanted with human fetal thymus and liver grafts (SCID-hu Thy/Liv mice) to KSHV infection. KSHV virions were inoculated directly into the implants, and viral DNA and mRNA production was assayed using real-time quantitative polymerase chain reaction. This revealed a biphasic infection, with an early phase of lytic replication accompanied and followed by sustained latency. Ultraviolet irradiation of the inoculum abolished all DNA- and mRNA-derived signals, and infection was inhibited by ganciclovir. Viral gene expression was most abundant in CD19+ B lymphocytes, suggesting that this model faithfully mimics the natural tropism of this virus. Short-term coinfection with HIV-1 did not alter the course of KSHV replication, nor did KSHV alter levels of HIV-1 p24 during the acute phase of the infection. Although no disease was evident in infected animals, SCID-hu Thy/Liv mice should allow the detailed study of KSHV tropism, latency, and drug susceptibility.
PMCID: PMC2195708  PMID: 10601360
Kaposi's sarcoma–associated herpesvirus; KSHV; SCID-hu; transmission; real-time PCR
4.  Human cytomegalovirus infection inhibits G1/S transition. 
Journal of Virology  1997;71(2):1629-1634.
Cell cycle progression during cytomegalovirus infection was investigated by fluorescence-activated cell sorter (FACS) analysis of the DNA content in growth-arrested as well as serum-stimulated human fibroblasts. Virus-infected cells maintained in either low (0.2%) or high (10%) serum failed to progress into S phase and failed to divide. DNA content analysis in the presence of G1/S (hydroxyurea and mimosine) and G2/M (nocodazole and colcemid) inhibitors demonstrated that upon virus infection of quiescent (G0) cells, the cell cycle did not progress beyond the G1/S border even after serum stimulation. Proteins which normally indicate G1/S transition (proliferating cell nuclear antigen [PCNA]) or G2/M transition (cyclin B1) were elevated by virus infection. PCNA levels were induced in infected cells and exhibited a punctate pattern of nuclear staining instead of the diffuse pattern observed in mock-infected cells. Cyclin B1 was induced in infected cells which exhibited a G1/S DNA content by FACS analysis, suggesting that expression of this key cell cycle function was dramatically altered by viral functions. These data demonstrate that contrary to expectations, cytomegalovirus inhibits normal cell cycle progression. The host cell is blocked prior to S phase to provide a favorable environment for viral replication.
PMCID: PMC191221  PMID: 8995690
5.  The 1993 Walter Hubert Lecture: the role of the p53 tumour-suppressor gene in tumorigenesis. 
British Journal of Cancer  1994;69(3):409-416.
The p53 tumour-suppressor gene is mutated in 60% of human tumours, and the product of the gene acts as a suppressor of cell division. It is thought that the growth-suppressive effects of p53 are mediated through the transcriptional transactivation activity of the protein. Overexpression of the p53 protein results either in arrest in the G1 phase of the cell cycle or in the induction of apoptosis. Both the level of the protein and its transcriptional transactivation activity increase following treatment of cells with agents that damage DNA, and it is thought that p53 acts to protect cells against the accumulation of mutations and subsequent conversion to a cancerous state. The induction of p53 levels in cells exposed to gamma-irradiation results in cell cycle arrest in some cells (fibroblasts) and apoptosis in others (thymocytes). Cells lacking p53 have lost this cell cycle control and presumably accumulate damage-induced mutations that result in tumorigenesis. Thus, the role of p53 in suppressing tumorigenesis may be to rescue the cell or organism from the mutagenic effects of DNA damage. Loss of p53 function accelerates the process of tumorigenesis and alters the response of cells to agents that damage DNA, indicating that successful strategies for radiation therapy may well need to take into account the tissue of origin and the status of p53 in the tumour.
PMCID: PMC1968876  PMID: 8123467
6.  Glue-sniffing neuropathies. 
Canadian Family Physician  1993;39:1965-1971.
The commonly used term for solvent abuse, glue sniffing, generally encompasses a variety of substances, including spray paint, thinners, nail varnish remover, gasoline, marking pens, and lighter fluids. Inhaled vapours eventually reach the lipids in the nervous system, where they can be stored for long periods. In three cases of glue-sniffing-related neurotoxicity, the peripheral nervous system was affected in two cases and predominantly the central nervous system in the third. Unfortunately follow up is difficult with this patient population and symptoms are often complicated by alcohol abuse.
Images
PMCID: PMC2379893  PMID: 8219845
7.  Complications of immobilization and bed rest. Part 2: Other complications. 
Canadian Family Physician  1993;39:1440-1446.
Prolonged immobilization affects almost every organ system. Respiratory complications include decreased ventilation, atelectasis, and pneumonia. Decreased basal metabolic rate, increased diuresis, natriuresis, and nitrogen and calcium depletion affect metabolism. Genitourinary problems include renal stones and more frequent urinary tract infections. Glucose intolerance, anorexia, constipation, and pressure sores might develop. Central nervous system changes could affect balance and coordination and lead to increasing dependence on caregivers.
Images
PMCID: PMC2379609  PMID: 8324412
8.  Complications of immobilization and bed rest. Part 1: Musculoskeletal and cardiovascular complications. 
Canadian Family Physician  1993;39:1428-1437.
Prolonged bed rest and immobilization inevitably lead to complications. Such complications are much easier to prevent than to treat. Musculoskeletal complications include loss of muscle strength and endurance, contractures and soft tissue changes, disuse osteoporosis, and degenerative joint disease. Cardiovascular complications include an increased heart rate, decreased cardiac reserve, orthostatic hypotension, and venous thromboembolism.
Images
PMCID: PMC2379624  PMID: 8324411

Results 1-8 (8)