A Study on the Association of Cytochrome-P450 1A1 Polymorphism and Breast Cancer Risk in North Indian Women

Cytochrome P-450 1A1 (CYP1A1) is involved in the 2-hydroxylation of estrogens and mammary carcinogens into 2-hydroxy catechol metabolites. Many commonly occurring single nucleotide polymorphism (SNP) are reported in CYP1A1 in various populations that include, isoleucine to valine substitution at 462 codon in heme binding region in exon 7 (A to G transition at position 2455; M2), threonine to asparagine substitution at codon 461 (C to A transversion at position 2453; M4), T to C transition at 3801 position (M1) and T to C transition at position 3205 (M3) in 3′ non-coding region. Epidemiological studies have shown inconsistent patterns between CYP1A1 polymorphism and breast cancer risk among various populations. Most of the studies have shown significant association between CYP1A1 genotype polymorphism and breast cancer risk. The present investigation was therefore undertaken to investigate the association of M1, M2, M3 and M4 polymorphisms and their subsequent contribution in premenopausal and postmenopausal women with breast cancer risk in north Indian women. Genomic DNA was isolated from case controls and breast cancer patients, specific segments of genomic DNA were amplified and restriction fragment length polymorphism (RFLP) was performed. CYP1A1 expression and catalytic activity were also assessed in premenopausal and postmenopausal case controls and patients. Polymorphism at M1, M2 and M4 alleles was detected and odds ratio for W/M1 and␣M1/M1 was calculated as 1.07 (95% CI, 0.59–1.87) and 0.74 (95% CI, 0.28–1.96) respectively. Odds ratio for W/M1 and M1/M1 alleles in premenopausal and postmenopausal women was 1.09 (95% CI, 0.45–2.49)/0.62 (95% CI, 0.10–2.66) and 1.60 (95% CI, 0.60–4.22)/1.06 (95% CI, 0.22–7.33) respectively. Odds ratio for W/M4 and M4/M4 allele was 1.20 (95% CI, 0.65–2.24)/4.55 (95% CI, 0.44–226.2) and 0.96 (95% CI, 0.36–2.64)/4.51 (95% CI, 0.23–273.0) respectively in total and premenopausal women. In postmenopausal women odds ratio was calculated as 1.16 (95% CI, 0.45–2.94) for M4/W but it could not be detected for M4/M4 since this genotype was not found in any postmenopausal case controls. Odds ratio for W/M2 genotype was calculated 0.57 (95% CI, 0.28–1.02), 1.06 (95% CI, 0.40–2.47) and 0.33 (95% CI, 0.12–0.89) respectively for total, premenopausal and postmenopausal women, however, in any group the odds ratio for M2/M2 could not be detected as M2/M2 genotype was not found in breast cancer patients. Polymorphism at M1 and M4 alleles was not found significantly associated with breast cancer risk and only wild type genotype was found in case controls and patients for M3 allele. Lack of protective association between CYP1A1 M2 genotype was also observed, however, in postmenopausal women a significant protective association with breast cancer risk was found (odds ratio, 0.33; 95% CI, 0.12–0.89; P-value 0.03). Similarly, no significant alteration in CYP1A1 expression and catalytic activity was observed in wild type and variant genotypes both in premenopausal and postmenopausal patients as compared with their respective controls. The results obtained from the present investigation thus suggest that probably CYP1A1 (M1, M2, M3, and M4) polymorphism alone does not play a significant role in the breast cancer risk in north Indian women.     

Letter to the Editor: Characterization of a Grapevine leafroll-associated virus 3 from India showing incongruence in its phylogeny

Survey conducted during 2010-2011 in the vineyards of Nashik and Pune regions of India revealed the association of an Ampelovirus antigenically related to Grapevine leafroll-associated virus 3 (GLRaV-3) with seven cultivars of grapevine. Upon sequencing of the coat protein (CP) and partial heat shock protein 70 homologue (HSP70h) genes of GLRaV-3 present in the cultivar Cabernet Souvignon showed distinct grouping behaviour. It clustered in group 2 and group 1 on the basis of CP and HSP70h sequences, respectively. Incongruent clustering pattern observed on the basis of two genomic regions suggest that GLRaV-3 is a distinct isolate from India.     

Supplemental maxillomandibular fixation with miniplate osteosynthesis��required or not?

Aim

To compare outcomes of open reduction and internal fixation of mandible fractures followed by either immediate mobilization or 5?days of maxillomandibular fixation.

Material and methods

We analyzed our use of supplemental maxillomandibular fixation with miniplate osteosynthesis during a 2.5-year period in 118 patients with 180 mandible fractures. A retrospective, matched pairing of identical fractures fixated with identical plating schemes was carried out. Thirty-five pairs of patients undergoing monocortical plating were identified. Patients in group 1 were treated with supplemental maxillomandibular fixation after surgery, whereas patients in group 2 (immediate release group) were treated without postoperative maxillomandibular fixation.

Results

The total rate of complications was 17% with supplemental maxillomandibular fixation and 14% without supplemental maxillomandibular fixation (p?>?0.05). No statistically significant outcome advantage could be attributed to the use of maxillomandibular fixation.

Conclusion

The current retrospective study shows no significant differences in treating isolated mandible fractures with open reduction and internal fixation and immediate release versus open reduction and internal fixation with 5?C7?days of MMF.     

Multi-spectral image analysis and classification of melanoma using fuzzy membership based partitions.

The sensitivity and specificity of melanoma diagnosis can be improved by adding the lesion depth and structure information obtained from the multi-spectral, trans-illumination images to the surface characteristic information obtained from the epi-illumination images. Wavelet transform based bi-modal channel energy features obtained from the images are used in the analysis. Methods using both crisp and fuzzy membership based partitioning of the feature space are evaluated. For this purpose, the ADWAT classification method that uses crisp partitioning is extended to handle multi-spectral image data. Also, multi-dimensional fuzzy membership functions with Gaussian and Bell profiles are proposed for classification. Results show that the fuzzy membership functions with Bell profile are more effective than the extended ADWAT method in discriminating melanoma from dysplastic nevus.     

The Fracture Toughness of Various Core Materials

Purpose This study determined the fracture toughness of four core buildup materials. Materials and Methods Single-edge notch, bar-shaped specimens conforming to the American Society for Testing Materials standard E-399 were fabricated for a high copper amalgam alloy, two composite resins, and a glass ionomer buildup material. The specimens were stored in air for 1 week and then tested in three-point bending mode with an Instron Universal Testing Machine (Instron Corporation, Canton, MA). Results Fracture toughness values obtained were as follows: Fluorocore (composite resin; Caulk, Milford, DE), 1.54 MN · m^?1.5; Ti-Core (composite resin and titanium; Essential Dental Systems, New York, NY), 1.34 MN · m^?1.5; Valiant Ph.D. (amalgam; Caulk), 1.29 MN · m^?1.5; and Coreshade Glass lonomer Base Cement (Shofu Inc, Kyota, Japan), 0.55 MN · m^?1.5. Conclusions Glass ionomer materials are probably unsuitable as core buildup materials because of their relatively low fracture toughness. Fluorocore, Ti-Core, and amalgam all had fracture toughness values significantly greater than the glass ionomer (P < .01).     

Presence of NMDA Receptor mRNA in the Anterior Pituitary of the Female Rat: Steroid Modulation and Changes during Gonadotropin Surge Induction

N-methyl- -aspartate (NMDA) receptors have been implicated in the regulation of anterior pituitary hormone secretion. A part of the regulatory effect of NMDA on pituitary hormone release could be due to a direct regulatory effect at the pituitary. The present study examined whether mRNA for the NMDA receptor is expressed in the anterior pituitary of female rats. Additionally, the effect of different steroids on pituitary NMDA receptor mRNA levels was also examined. Using Northern analysis, hybridization of the NMDA R1 cDNA probe to female rat anterior pituitary RNA yielded a 4.0-kb band, demonstrating the presence of the mRNA for the NMDA receptor in the pituitary. In the ovariectomized immature rat, estradiol treatment was found to significantly suppress pituitary NMDA receptor mRNA levels. Conversely, pituitary NMDA receptor mRNA levels were elevated by the treatment of estrogen-primed ovariectomized rats with progesterone. The increase of pituitary NMDA receptor mRNA levels by progesterone occurred at a time when progesterone induces an LH surge. Using the pregnant mare serum gonadotropin-primed immature rat, pituitary NMDA receptor mRNA levels were found to increase in a progressive manner throughout the afternoon of proestrus to reach a peak at 2000 h—the time of peak preovulatory LH surge levels. In conclusion, the present study demonstrates that the mRNA for the NMDA receptor is expressed in the anterior pituitary. The NMDA receptor mRNA in the pituitary is regulated by steroids with peak levels paralleling gonadotropin surge expression. As a whole, the present study provides further evidence that the pituitary could be an important site of action for neuroendocrine effects of excitatory amino acids.