Blur adaptation: clinical and refractive considerations

The human visual system is amenable to a number of adaptive processes; one such process, or collection of processes, is the adaptation to blur. Blur adaptation can be observed as an improvement in vision under degraded conditions, and these changes occur relatively rapidly following exposure to blur. The potential important future directions of this research area and the clinical implications of blur adaptation are discussed.     

Association of a common polymorphism in the cyclooxygenase 2 gene with risk of non-small cell lung cancer

Carcinogenesis, 25, 229–235, 2004 We reported the association of     

Biomonitoring of genotoxic exposure of aluminium plant workers.

Humans are environmentally and occupationally exposed to polycyclic aromatic hydrocarbons (PAH). PAH's are a class of tumorigenic compounds which act through metabolic transformation to chemically reactive forms, epoxides, which covalently bind to DNA forming DNA adducts. To evaluate the genotoxic effects of PAH's, air and urine samples were analyzed for PAH. Blood samples were analyzed for benzo(a)pyrene-diol-epoxide-DNA (BPDE-DNA) adducts. New methods for analyzing DNA adducts in lymphocytes have been used to study the genotoxic effects of human exposure to carcinogens. BPDE-DNA adducts in lymphocytes have been used as internal dosimeters of exposure to PAH's and several studies have been conducted. We measured BPDE-DNA adducts in aluminium plant workers with immuno-assay and physico-chemical methods. PAH-DNA adducts were detectable to a lesser extent in subjects working in an aluminium plant compared to subjects working in a coke oven plant.     

The Frequency of Human Papillomavirus Detection in Postmenopausal Women on Hormone Replacement Therapy

Postmenopausal women enrolled in the Iowa portion of the postmenopausal estrogen/progestin interventions randomized clinical trial (n= 105) during 1989–1991 were studied for (i) the prevalence of human papillomavirus (HPV) in this older age population (ages 45–64), and (ii) the association between hormone replacement therapies (HRTs) and changes in detection of HPV over a 2-year time period. HPV is causative in most cervical and some other genital cancers and in the presence of steroid hormones has been shown to increase neoplastic transformation by HPVin vitro.Using PCR to detect HPV DNA, the overall frequency of the virus regardless of time period was 50.3% (n= 53) with a baseline (BL) frequency of 38.1% and the second year follow-up (FU) of 22.9%. The oncogenic types HPV-16 (75.5%) and HPV-31 (20.8%) were the most commonly reported. All those with persistently detected infection (10.5%), defined as HPV+ at both BL and FU, were identified with HPV-16 or -18. Between these two time periods there were no significant differences in HPV frequency between the placebo and combined HRT groups (BL−/FU+, 21% vs 18%; BL+/FU−, 71% vs 80%). While the study is based on a small sample, the findings suggest that short-term use of HRTs is not associated with an increased risk of HPV detection, but assessment of effects from long-term use is needed. The data also indicate that the frequency of HPV found in older women is higher than previously suspected but that short-term changes in HPV detected in this age group are unrelated to the development of precancerous cervical lesions.     

Serum ionic fluoride levels in haemodialysis and continuous ambulatory peritoneal dialysis patients

High serum fluoride (F-) in patients with chronic renal failure (CRF) and end-stage renal disease (ESRD) is associated with risk of renal osteodystrophy and other bone changes. This study was done to determine F- in normal healthy controls and patients with ESRD on haemodialysis (HD) or peritoneal dialysis (PD). Seventeen healthy controls (12 males, 5 females) and 39 ESRD patients on dialysis (17 males, 22 females) were recruited in the study in a community with 47.4 +/- 3.28 microM/l (range 44-51 microM/l) of F- content in drinking water. Control subjects showed a mean serum F- concentration of 1.08 +/- 0.350 microM/l. Males in control group showed slightly higher F- levels (1.15 +/- 0.334, range 0.55-1.9 microM/l) than females (0.92 +/- 0.370, range 0.6-1.5 microM/l). Mean serum F- concentration did not correlate significantly with age and sex among control subjects, whereas such correlation was observed in patients with ESRD on dialysis. Mean serum F- concentration was significantly higher in patients on dialysis (2.67 +/- 1.09, range 0.8-5.2 microM/l) than normal controls. When grouped according to sex, the mean serum F- concentration in males (3.05 +/- 1.04, range 1.8-5.2 microM/l) was significantly higher than females (2.38 +/- 1.08, range 0.8-5.2 microM/l). When patients were grouped according to age, it was observed that F- concentration was significantly higher in patients with age groups 21-70 (2.86 +/- 1.05) than those with age group 13-20 years (1.42 +/- 0.531). Thus F- concentration correlated with age and sex, being higher in males and above 20 years. Despite appreciable clearance of F- (39-90%) across the peritoneum, patients on CAPD showed higher serum F- concentration than those on HD (3.1 +/- 1.97 vs 2.5 +/- 1.137 microM/l). Of the total 39 patients on dialysis 39% had their serum F- concentration above 3.0 microM/l, posing the risk of renal osteodystrophy.      

Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability

X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG repeat expansion in the first exon of the androgen receptor (AR) gene. Disease-associated alleles (37-66 CAGs) change in length when transmitted from parents to offspring, with a significantly greater tendency to shift size when inherited paternally. As transgenic mice carrying human AR cDNAs with 45 and 66 CAG repeats do not display repeat instability, we attempted to model trinucleotide repeat instability by generating transgenic mice with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions in their genomic context. Studies of independent lines of AR YAC transgenic mice with CAG 45 alleles reveal intergenerational instability at an overall rate of approximately 10%. We also find that the 45 CAG repeat tracts are significantly more unstable with maternal transmission and as the transmitting mother ages. Of all the CAG/CTG repeat transgenic mice produced to date the AR YAC CAG 45 mice are unstable with the smallest trinucleotide repeat mutations, suggesting that the length threshold for repeat instability in the mouse may be lowered by including the appropriate flanking human DNA sequences. By sequence-tagged site content analysis and long range mapping we determined that one unstable transgenic line has integrated an approximately 70 kb segment of the AR locus due to fragmentation of the AR YAC. Identification of the cis - acting elements that permit CAG tract instability and the trans -acting factors that modulate repeat instability in the AR YAC CAG 45 mice may provide insights into the molecular basis of trinucleotide repeat instability in humans.