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1.  Exploiting inflammation for therapeutic gain in pancreatic cancer 
British Journal of Cancer  2013;108(5):997-1003.
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy associated with <5% 5-year survival, in which standard chemotherapeutics have limited benefit. The disease is associated with significant intra- and peritumoral inflammation and failure of protective immunosurveillance. Indeed, inflammatory signals are implicated in both tumour initiation and tumour progression. The major pathways regulating PDAC-associated inflammation are now being explored. Activation of leukocytes, and upregulation of cytokine and chemokine signalling pathways, both have been shown to modulate PDAC progression. Therefore, targeting inflammatory pathways may be of benefit as part of a multi-target approach to PDAC therapy. This review explores the pathways known to modulate inflammation at different stages of tumour development, drawing conclusions on their potential as therapeutic targets in PDAC.
PMCID: PMC3619061  PMID: 23385734
pancreatic cancer; inflammation; therapy
2.  Meta-analysis of genome-wide association data detects a risk locus for major mood disorders on chromosome 3p21.1 
Nature genetics  2010;42(2):128-131.
The major mood disorders, which include bipolar disorder (BD) and major depressive disorder (MDD), are substantially heritable, but few risk loci have been identified. We performed a meta-analysis of 5 major mood disorder case-control samples, including over 13,600 unique individuals genotyped with approximately 500,000 to 1 million single nucleotide polymorphism (SNP) markers on high-density arrays. Allele-wise association results were meta-analyzed with a method that weights results by sample size. We found genome-wide significant evidence that SNPs in a region of chromosome 3p21.1were associated with major mood disorders. The SNP rs2251219 returned the smallest meta-analysis p-value, 3.63 × 10−8, with a pooled odds ratio of 0.87. Supportive results were observed in 2 out of 3 independent samples tested in a replication study. These results implicate one or more genes in this region in the etiology of major mood disorders and suggest that BD and MDD share genetic risk factors.
PMCID: PMC2854040  PMID: 20081856
bipolar; depression; GAIN; STAB1; NT5DC2; PBRM1; NEK4; SPCS1; GNL3; GLT8D1; ITIH
3.  Evidence-Based Interventions and Screening Recommendations for Colorectal Cancer in Comprehensive Cancer Control Plans: A Content Analysis 
Preventing Chronic Disease  2009;6(4):A127.
Colorectal cancer is the third most commonly diagnosed cancer and third leading cause of cancer death in the United States. The extent to which Comprehensive Cancer Control (CCC) programs in states, tribal governments and organizations, territories, and Pacific Island jurisdictions address evidence-based recommendations and interventions for colorectal cancer in their CCC plans is largely unknown.
We downloaded CCC plans posted on the Cancer Control PLANET Web site for review. We searched the plans for key terms, identifying potential evidence-based content surrounding colorectal cancer prevention and early detection. Content was abstracted for further review and classification.
Of 55 plans reviewed, 54 (98%) referred to evidence-based recommendations or interventions for colorectal cancer or indicated they intended to refer to the evidence base when developing programs. More than 57% (n = 31) of programs referred to the American Cancer Society guidelines, 41% (n = 22) referred to the United States Preventive Services Task Force, and 11% (n = 6) referred to the Guide to Community Preventive Services. Few programs mentioned Research Tested Intervention Programs (n = 1), National Cancer Institute's Physician Data Query (n = 4), Cochrane Reviews (n = 2), or Put Prevention Into Practice (n = 2) in reference to evidence-based interventions for colorectal cancer prevention.
Most CCC programs discussed either evidence-based screening guidelines or interventions in their cancer plans, although many mentioned this information exclusively as background information. We recommend that program planners be trained to locate evidence-based interventions and use consistent common language to describe them in their plans. CCC program planners should be encouraged to conduct and publish intervention studies.
PMCID: PMC2774641  PMID: 19755003
4.  Oral and vaginal epithelial cell anti-Candida activity is acid labile and does not require live epithelial cells 
Oral microbiology and immunology  2005;20(4):199-205.
Background: Candida albicans is the causative agent of oral and vaginal candidiasis. Innate host defenses against C. albicans are important against each infection. Among these are oral and vaginal epithelial cells that have anti-Candida activity. The mechanism of action includes a requirement for cell contact with no role for soluble factors, and a putative role for carbohydrates based on the sensitivity of the activity to periodic acid.
Methods: Periodic acid treatment of epithelial cells as well as the property of partial resistance of antifungal activity to fixation was used to further dissect the mechanism of action.
Results: The results herein effectively now challenge a role for carbohydrates alone. Firstly, the putative carbohydrate(s) released into supernatants of periodic acid-treated epithelial cells could not compete with fresh epithelial cells for activity, and equivalent abrogation of activity was observed by periodic acid-treated cells irrespective of the amount of carbohydrate released. Instead, the similar abrogation of activity following treatment with other acids or when cocultured under acidic conditions suggests that the activity is acid-labile. Finally, while activity requires intact epithelial cells, it does not require live cells; activity was minimally affected by fixing epithelial cells prior to coculture where the majority of cells remained impermeable to Trypan blue but were defined as non–viable by positive nuclear staining with propidium iodide.
Conclusion: These results suggest that antifungal activity is dependent on contact by intact, but not necessarily live, epithelial cells through an acid-labile mechanism.
PMCID: PMC1361270  PMID: 15943762
Candida albicans; epithelial cells; innate immunity; oral mucosa; vaginal mucosa
6.  HIV/AIDS among minority races and ethnicities in the United States, 1999-2003. 
BACKGROUND: During June 1981 to June 1982, 37% of more than 400 cases of AIDS reported to the CDC were in minority races and ethnicities. In 2003, 72% of the estimated 43,171 cases of AIDS diagnosed in the 50 states; District of Columbia; and U.S. dependencies, possessions and free nations were in minority races and ethnicities. METHODS: We analyzed HIV/AIDS data for 2000-2003 reported by the 32 states that have had confidential name-based reporting of HIV infection since 1999. For analysis of AIDS data, we used data for 1999-2003 reported by the 50 states and the District of Columbia. HIV/AIDS and AIDS data were statistically adjusted for reporting delays and redistribution of cases initially reported without risk factors. RESULTS: For all years, the numbers of HIV/AIDS and AIDS diagnoses were consistently higher among non-Hispanic blacks than among other races and ethnicities. In the 32 states with HIV reporting, the HIV/AIDS diagnosis rate in 2003 was 74 per 100,000 for blacks, 25 per 100,000 for Hispanics, 11 per 100,000 for American Indians/Alaska Natives, nine per 100,000 for whites, and seven per 100,000 for Asians/Pacific Islanders. The rates for persons living with HIV/AIDS at the end of 2003 were highest for blacks (765 per 100,000) and Hispanics (220 per 100,000). In the 50 states and the District of Columbia, AIDS diagnosis rates in 2003 were 58 per 100,000 for blacks, 20 per 100,000 for Hispanics, eight per 100,000 for American Indians/Alaska Natives, and four per 100,000 for Asians/Pacific Islanders. CONCLUSION: HIV/AIDS disproportionately affects minority races and ethnicities in the United States. To reduce rates of HIV/AIDS in these populations, effective and culturally appropriate prevention interventions must be developed and implemented.
PMCID: PMC2640648  PMID: 16080451
7.  Kinematic analysis of shear displacement as a means for operating mechanotransduction channels in the contact region between adjacent stereocilia of mammalian cochlear hair cells. 
In sensory hair cells of the cochlea, deflection of the stereociliary bundle results in direct mechanical gating of mechanoelectrical transduction channels, a function generally attributed to the tip link running between the tips of short stereocilia and the sides of adjacent taller ones. However, immunocytochemical experiments indicate that the channels may not be associated with the tip link but occur just below it in a region of contact between the stereocilia. To determine whether transduction channels in this location could be operated during physiologically appropriate deflections as effectively by shear displacement as if they were associated with the tip link, a two dimensional kinematic analysis of relative motion between stereocilia has been performed assuming contact between stereocilia is maintained during deflection. Bundle geometry and dimensions were determined from transmission electron micrographs of hair cells from several frequency locations between 0.27 and 13.00 kHz in the guinea-pig cochlea. The analysis indicates that for a 10 nm deflection of the tallest stereocilia of both inner and outer hair cells, i.e. within the range of the maximum sensitivity of mammalian hair bundles, the average shear displacement in the contact region would be 1.6 nm, but that it increases systematically towards higher frequency regions for outer hair cells. This displacement is comparable in magnitude to tip-link elongation for individual stereociliary pairs.
PMCID: PMC1688222  PMID: 9061959
8.  Deep corneal stromal opacities associated with long term contact lens wear. 
BACKGROUND: One male and three female long term contact lens wearers (mean age 30.3 years; range 26-33) demonstrated unusual deep corneal stromal opacities which were predominantly just anterior to Descemet's membrane. None had any history of corneal dystrophy. These opacities were more common centrally, but were also identified in the corneal periphery. METHODS: All patients underwent routine ophthalmic examinations and, where appropriate, slit-lamp photography and specular microscopy. RESULTS: Mean lens wear in years and hours per day was 14.3 (range 10-17) and 14.3 (range 12-16) respectively. Specular microscopy disclosed cell densities within normal limits (mean 3041.5 cells per mm2) and coefficient of variation of mean cell area; COV = 0.31. Refractive errors ranged from -12.25 D to +6.25 best vision sphere and all four subjects attained at least 6/9 Snellen visual acuity. The subjects' contact lens wearing history included low water content hydroxymethylmethacrylate (HEMA) contact lenses and high water content HEMA contact lenses. Stromal opacity density was observed to diminish over a period of months on cessation of contact lens wear in two cases. CONCLUSION: The possible causes of these rarely reported opacities are discussed.
PMCID: PMC505377  PMID: 8664225
9.  Origin of disc new vessels assessed by videofluorography. 
Ten patients with disc neovascularisation of various aetiologies were studied to ascertain the origin of their new vessels. Fluorescein angiography was carried out with an image intensified video camera. A retinal artery derivation was demonstrated for the first time and was seen in three cases. Six further patients showed a retinal venous supply, and finally there was one from a choroidal source.
PMCID: PMC1041462  PMID: 2456094
10.  Functional capacity of marginated and bone marrow reserve granulocytes. 
Infection and Immunity  1987;55(10):2359-2363.
Marginated and bone marrow reserve granulocytes were obtained from young healthy volunteers after subcutaneous administration of aqueous epinephrine (0.4 ml/m2) or intravenous administration of hydrocortisone sodium succinate (250 mg), respectively. These leukocytes were compared with circulating granulocytes for the ability to adhere to surfaces, migrate in a random fashion, respond to chemoattractants, interact with autologous serum opsonins, and phagocytize and kill five common bacterial pathogens. As contrasted with circulating neutrophils, marginated cells had enhanced phagocytic and killing capacity for some pathogens, whereas adherence, random migration, chemotaxis, and chemiluminescence for the two cell populations were equivalent. Bone marrow reserve cells demonstrated increased activity for three functional mechanisms; chemotaxis for these cells averaged 21% higher than that for circulating cells, and phagocytosis was 32% higher, with 6 to 17% greater killing of the five bacterial species studied. All of these differences were statistically significant (P less than 0.05). Random migration and interaction with serum opsonins were unchanged in bone marrow granulocytes. These enhanced functional properties of neutrophils which are outside of the circulating pool may represent important host defense mechanisms during episodes of bacterial infection.
PMCID: PMC260713  PMID: 3653982
11.  Traumatic myopia; an ultrasonographic and clinical study. 
Three patients with transient myopia following blunt injury are described with the aid of serial ultrasonography. The cause of refractive change is an increase in the anteroposterior thickness of the crystalline lens, which probably results from oedema of the ciliary body.
PMCID: PMC1041147  PMID: 3555608
12.  Leukocyte survival in cerebrospinal fluid. 
Journal of Clinical Microbiology  1986;23(5):965-966.
Delays in the laboratory examination of cerebrospinal fluid are commonly encountered in clinical medicine. The present studies were designed to evaluate changes in cerebrospinal fluid leukocyte counts relative to time elapsed before analysis. Neutrophil counts decreased most rapidly, being 68 +/- 10% (standard error of the mean) and 50 +/- 12% of initial values at 1 and 2 h, respectively. Lymphocyte and monocyte numbers were not significantly altered until 3 h.
PMCID: PMC268763  PMID: 3711287
13.  A comparison of the frequency of major affective disorder in Huntington's disease and Alzheimer's disease. 
Matched groups of patients suffering from Huntington's disease and Alzheimer's disease were compared for psychiatric morbidity prior to the onset of dementia. The Huntington's disease group showed twice the incidence of major affective disorder. This finding suggests a specific relationship between Huntington's disease and major affective disorder rather than the latter being a non-specific prodromal feature of dementia.
PMCID: PMC1028580  PMID: 2934517
14.  Culture of the surfaces of urinary catheters to sample urethral flora and study the effect of antimicrobial therapy. 
Journal of Clinical Microbiology  1985;21(6):902-908.
At the time indwelling urinary catheters were removed, the urethral flora was sampled by rolling the catheters onto culture plates. Cultures were obtained from 398 patients with sterile urine. Catheter surfaces were colonized less often in males than in females (16.8 and 67.0%, respectively) and yielded correspondingly fewer bacterial species per catheter. In both sexes, gram-positive species were isolated more frequently than gram-negative species (428 and 131 isolates, respectively). The bacteria most commonly isolated were Staphylococcus epidermidis and Streptococcus faecalis. Staphylococcus saprophyticus was not recovered despite the large proportion of young, sexually active women in the study population. Gram-negative bacteria, mainly Escherichia coli, gradually colonized the catheters over time but at all times were recovered in lower amounts the gram-positive organisms and less often in males than in females. Slime production by coagulase-negative staphylococci did not relate to the density of organisms recovered from the catheters or influence the presence of gram-negative bacteria. Despite frequent use of antibiotics in this population, the urethral flora remained highly susceptible to these drugs. Antibacterial activity was not detected on the catheters despite high concentrations in the urine. This suggests that systemic antibiotics have a very limited effect on resident urethral flora. Despite relatively small numbers in the urethra, gram-negative bacteria readily produce urinary tract infections in catheterized patients.
PMCID: PMC271815  PMID: 4008620
15.  Endophthalmitis due to caterpillar setae: surgical removal and electron microscopic appearances of the setae. 
A case of endophthalmitis due to caterpillar setae was, for the first time, successfully treated by surgical removal of the setae. The procedure was facilitated by the use of sodium hyaluronidate. Scanning and transmission electron microscopy of the setae showed evidence of enzymatic degradation of the shaft and burial of the spines in exudate.
PMCID: PMC1040315  PMID: 6608373
16.  Treatment of vaginal candidosis with econazole nitrate and nystatin 
A study carried out to compare the efficacy of econazole nitrate and nystatin in the treatment of vaginal candidosis showed that a three-day course of econazole nitrate pessaries was as effective as a 14-day course of nystatin pessaries and is more acceptable to patients.
PMCID: PMC1045918  PMID: 7237085
19.  Thumb-sucking and the Teeth 
British Medical Journal  1965;2(5458):422.
PMCID: PMC1845439  PMID: 20726048

Results 1-23 (23)