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1.  Translational and Clinical Applications of Salivary Diagnostics 
Advances in Dental Research  2011;23(4):375-380.
There have been significant advances in techniques for the detection of biomarker signals in the oral cavity (e.g., ELISAs for proteins, PCR for RNA and DNA) as well as the engineering and development of microfluidic approaches to make oral-based point-of-care (POC) methods for the diagnosis for both local and systemic conditions a reality. In this section, we focus on three such approaches, namely, periodontal disease management, early markers for systemic diseases, and salivary markers useful for pharmacogenomic studies. Novel approaches using non-invasive, salivary samples and user-friendly devices offer results that are as sensitive and specific as laboratory-based analyses using blood or urine.
PMCID: PMC3172998  PMID: 21917748
biomarkers; saliva; cardiovascular disease; pharmacogenomics; periodontal diseases; lab-on-a-chip
2.  Thyroid dysfunction can predict response to immunotherapy with interleukin-2 and interferon-2 alpha. 
British Journal of Cancer  1991;64(5):915-918.
Thyroid dysfunction is a well-recognised side-effect of treatment with interleukin-2 (IL2). We assessed the correlation between the development of abnormal thyroid function and tumour response in 13 patients receiving IL2 and interferon-2 alpha (IFN2 alpha) for advanced malignancy. Seven patients had normal thyroid function during treatment, and all of these patients have since died of progressive disease. Of six patients who did develop thyroid dysfunction during treatment, one patient has died of progressive disease. However, statistically we were unable to confirm a definite correlation between the development of thyroid dysfunction and survival in this small group of patients.
PMCID: PMC1977462  PMID: 1931616
3.  Airborne influenza virus detection with four aerosol samplers using molecular and infectivity assays: considerations for a new infectious virus aerosol sampler 
Indoor air  2009;19(5):433-441.
As a first step in conducting studies of airborne influenza transmission, we compared the collection performance of an SKC Biosampler, a compact cascade impactor (CCI), Teflon filters, and gelatin filters by collecting aerosolized influenza virus in a one-pass aerosol chamber. Influenza virus infectivity was determined using a fluorescent focus assay and influenza virus nucleic acid (originating from viable and non-viable viruses) was measured using quantitative PCR. The results showed that the SKC Biosampler recovered and preserved influenza virus infectivity much better than the other samplers – the CCI, Teflon, and gelatin filters recovered only 7–22% of infectious viruses compared with the Biosampler. Total virus collection was not significantly different among the SKC Biosampler, the gelatin, and Teflon filters, but was significantly lower in the CCI. Results from this study show that a new sampler is needed for virus aerosol sampling, as commercially available samplers do not efficiently collect and conserve virus infectivity. Applications for a new sampler include studies of airborne disease transmission and bioterrorism monitoring. Design parameters for a new sampler include high collection efficiency for fine particles and liquid sampling media to preserve infectivity.
PMCID: PMC3684270  PMID: 19689447
Influenza; Air sampler; Biosampler; Compact Cascade Impactor; Teflon filter; Gelatin filter
4.  Effects of tumour necrosis factor-α on BrdU incorporation in cultured human enterocytes 
Mediators of Inflammation  1995;4(1):31-37.
Bromodeoxyuridine incorporation is a useful method for studying the pattern of DNA synthesis in proliferating cells. The distribution pattern of incorporated BrdU in villus enterocytes of duodenal explants was analysed after exposure to TNFα in organ culture. TNFα caused a consistent, low level uptake of BrdU in the portion of the nucleus close to the nuclear membrane, this pattern was absent from the control cultures. As these epithelial cells are terminally arrested in G0, the BrdU incorporation was thought not to be due to S phase DNA synthesis, but rather a response to the cytotoxic influence of TNFα. Microtitre plate proliferation assays of cell density and DNA synthesis were devised to study the effects of TNFα on confluent monolayers of the human foetal jejunal cell line I407 and the mouse fibrosarcoma cell line L929. Both cell lines showed a similar response to TNFα. Exposure to TNFα alone did not reduce cell numbers but did cause a significant increase in DNA synthesis (p < 0.05). When cycloheximtde was added in tandem with TNFα there was a significant reduction in cell number (p < 0.001) and level of DNA synthesis (p < 0.01) indicative of cell death. The DNA of cells exposed to TNFα and cycloheximide was fragmented when viewed on an electrophoresis gel. The results show that BrdU incorporation might be a good indicator of damage to the DNA of cells after cytotoxic insult. TNFα may be responsible for villus enterocyte damage in enteropathies such as coeliac disease and GVHR of the small bowel.
PMCID: PMC2365608  PMID: 18475613
5.  Tyrosine phosphorylation in the human duodenum. 
Gut  1995;36(1):34-38.
Many growth factor receptors including the epidermal growth factor receptor function through tyrosine kinase activity. The aim of this study was to examine the constitutive level of tyrosine phosphorylation in the normal duodenum and in the hyperproliferative coeliac duodenum. A flow cytometric assay was devised using monoclonal antibody to phosphorylated (but not native) tyrosine residues to determine the levels of tyrosine phosphorylation in both CD3 positive intraepithelial lymphocytes and CD3 negative epithelial cells obtained by EDTA treatment of endoscopically obtained duodenal biopsy specimens. In addition, immunohistochemistry was performed on 18 formalin fixed coeliac duodenal biopsy specimens and eight control specimens. Tyrosine phosphorylation could be detected by flow cytometry on duodenal enterocytes and this expression was up regulated by pretreatment with epidermal growth factor. Tyrosine phosphorylation decreased with progression from the villus to the crypt, however, and was virtually undetectable on crypt enterocytes. Immunohistochemistry of the coeliac duodenum showed virtually absent tyrosine phosphorylation in the crypt. Increased tyrosine phosphorylation was detected in the infiltrating T cells. In conclusion, tyrosine phosphorylation in the duodenum is confined to the non-proliferative villous epithelium and is virtually undetectable in the proliferative crypt compartment. These findings suggest that tyrosine kinase activity is not a significant factor in the regulation of crypt cell proliferation in the human duodenum either in normal subjects or in coeliac disease patients.
PMCID: PMC1382349  PMID: 7534252
6.  Gastric T lymphocyte responses to Helicobacter pylori in patients with H pylori colonisation. 
Gut  1994;35(10):1379-1384.
Helicobacter pylori has been identified as a dominant factor in the pathogenesis of duodenal ulcer. The aim of this study was to examine peripheral blood and gastric lymphocyte proliferation and cytokine production in patients with H pylori colonisation. Sixty five dyspeptic patients attending for endoscopy were studied; 35 of these were H pylori positive and 30 H pylori negative as assessed by culture, histology, and rapid urease test. H pylori antigen was capable of stimulating peripheral blood lymphocyte proliferative responses even in H pylori negative patients. Peripheral blood lymphocyte proliferative responses to H pylori (but not to purified protein derivative or phythaemagglutinin) were significantly lower in H pylori positive than H pylori negative patients. Similarly, antigen specific proliferative responses and interferon gamma production by gastric lamina propria lymphocytes were also depressed in H pylori positive patients compared with H pylori negative patients. CD8 and CD22 positive lamina propria lymphocytes were increased in H pylori positive patients. These data show that antigen specific responses to H pylori are significantly lower in H pylori positive patients and could indicate activation of antigen specific suppression.
PMCID: PMC1375009  PMID: 7959191
7.  Coagulopathy associated with extended-spectrum cephalosporins in patients with serious infections. 
Patients enrolled in two double-blind multicenter studies were evaluated for the development of hypoprothrombinemia during treatment with cephalosporins. Patients with pneumonia or peritonitis received ceftizoxime, cefotaxime, or moxalactam. The incidence of hypoprothrombinemia was greater in patients with peritonitis (12 of 49) than in those with pneumonia (5 of 96; P less than 0.05). Overall, moxalactam was associated with a higher incidence of hypoprothrombinemia (13 of 52) than either ceftizoxime (1 of 43; P less than 0.05) or cefotaxime (3 of 50; P less than 0.05), and moxalactam patients incurred the highest average increase in prothrombin time (3.7 s) as compared with either ceftizoxime (0.5 s; P less than 0.05) or cefotaxime (0.9 s; P less than 0.05) patients. The occurrence of hypoprothrombinemia in moxalactam patients with peritonitis was not related to dosage, duration of therapy, age, sex, race, or renal or hepatic function. The degree of ileus was, however, strongly related to the development of coagulopathy in moxalactam-treated patients only.
PMCID: PMC174706  PMID: 3471181

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