Molecular epidemiologic studies of polycyclic aromatic hydrocarbon-DNA adducts and breast cancer

We review our studies on the role of polycyclic aromatic hydrocarbon (PAH)-DNA adducts in breast cancer. Additionally we report on analyses of the reliability of the scoring procedures used with immunohistochemical assay for PAH-DNA adducts and of potential bias arising from the use of benign breast disease (BBD) controls. We conducted a case-control study utilizing two control groups: BBD controls who donated tissue and blood samples, and healthy controls who donated blood samples. In comparisons of tumor tissue from cases and benign tissue from BBD controls, increasing adduct levels were significantly associated with case-control status [odds ratio (OR) = 2.40, 95% confidence interval (CI) 1.18-4.92], whereas in comparisons of nontumor tissue from cases and benign tissue from BBD controls the association was nonsignificant (OR = 1.97, 95% CI 0.94-4.17). We also show among cases, but not among BBD controls, that the GSTM1 null genotype is associated with increased adduct levels in breast tissue. Our reliability study found the scoring procedures used with the immunohistochemical assay to have high reliability, 0.93 in nontumor, 0.82 in tumor, and 0.74 in benign tissues. However, we found that the technician significantly contributed to the total variability of a series of data. Finally, we did not find a consistent bias to the null associated with the use of BBD controls; however, BBD controls may overestimate the prevalence of family history of breast cancer compared to that of healthy controls (18% vs.14%). We hypothesize that the higher prevalence results from a referral bias and discuss how this may influence our results.     

Role of persistent amenorrhea in bone mineral metabolism of young hemodialyzed women

BACKGROUND: Chronic renal failure in women is frequently associated with endocrine disturbances leading to menstrual disorders. However, most studies on renal osteodystrophy have not taken into account the possible role of these hormonal disturbances on the pathogenesis of bone alterations seen in these patients. In the present study, we evaluated bone mineral metabolism in a group of young hemodialyzed women with persistent amenorrhea and compared them with similar women with regular menstruation. METHODS: We studied 74 women who were further subdivided into 43 women with regular menstrual periods and 31 women with persistent amenorrhea, defined as the absence of menstrual bleeding for more than six months. In all patients, we performed a bone mineral density (BMD) analysis and simultaneously evaluated different biochemical parameters, intact parathyroid hormone (iPTH), sexual hormone determinations that included total estradiol, follicle-stimulating (FSH), and luteinizing hormone and markers of bone resorption such as the procollagen type 1 cross-linked carboxy-terminal telopeptide (ICTP). RESULTS: Serum calcium, phosphorus, and iPTH were similar in both groups. Serum alkaline phosphatase was higher in amenorrheic women. Although the total serum estradiol concentration was normal in the amenorrheic women when compared with nonuremic women, the values were significantly lower than those in regularly menstruating women. Serum FSH and ICTP values were significantly higher in the amenorrheic women. Trabecular BMD in the lumbar spine was also significantly lower in the amenorrheic women compared with regularly menstruating dialysis patients. Lumbar spine BMD and total estradiol levels correlated significantly in the amenorrheic group. CONCLUSIONS: These studies show that persistent amenorrheic young women on dialysis have lower trabecular BMD and evidence of increased bone resorption when compared with normal menstruating women on dialysis. The possible impact of these results in the natural history of the uremic osteodystrophy remains to be determined.     

Factors linked to disease severity and time to remission in patients with chronic spontaneous urticaria

Biomarkers useful for the evaluation and management of patients with chronic spontaneous urticaria (CSU) are not currently available. A review of various clinical and laboratory markers that have been studied to assess their value for determining the severity or predicting the evolution of disease in adult patients with CSU was carried out. A search of the medical literature on PubMed and MEDLINE including the terms urticaria, chronic urticaria, chronic idiopathic urticaria, CSU, severity, prognosis and treatment was performed. Based on our review of the literature, among the clinical markers studied, higher age at onset, being female, long disease duration and aspirin/NSAID hypersensitivity may be linked to both severe CSU and a long time to spontaneous remission. In addition, a positive autologous serum skin test (ASST) may be associated with severe CSU, and comorbidity of inducible urticaria and concomitant recurrent angio‐oedema may be linked to longer CSU duration. Potential biomarkers of CSU severity and/or duration include basophil numbers and susceptibility to activation, inflammatory markers, markers of activation of the extrinsic coagulation pathway, immunoglobulin E and vitamin D. Although the described markers are promising, further studies on representative and well‐characterized patient populations are needed to determine the value of these clinical and biological markers for predicting the severity and course of disease in patients with CSU.     

A brain‐potential correlate of task‐set conflict

Brain‐potential correlates of response conflict are well documented, but those of task conflict are not. Task‐switching studies have suggested a plausible correlate of task conflict—a poststimulus posterior negativity—however, in such paradigms the negativity may also reflect poststimulus task‐set reconfiguration postulated in some models. Here, participants alternated between single‐task blocks of classifying letters and digits; hence, no within‐block task‐set reconfiguration was required. Presenting letters alongside digits slowed responses to the digits and elicited an ERP negativity from ～350 ms, relative to task‐neutral symbols presented alongside digits, consistent with task conflict. The negativity was also present for congruent digit‐letter stimuli; this and the lack of behavioral response congruency effects indicate conflict at the level of task‐set rather than response selection.     

Maternal psychological growth following childbirth

Although maternal postpartum mental health has been extensively studied, rather little is known regarding the factors that may facilitate psychological growth following childbirth. The present study set forth to examine various pre-birth, birth, and post-birth correlates of overall psychological growth and growth domains in postpartum women, assessed within the first months following childbirth. A sample of 428 women completed self-report measures pertaining to psychological growth, mental health, maternal attachment, and childbirth characteristics. We found that the majority of women reported psychological growth following childbirth, with those experiencing stressors in childbirth reporting the highest levels of appreciation for life. In regression analyses, postpartum factors were significantly associated with overall growth and growth domains, taking into account other factors. The more the childbirth was perceived as central to the mothers’ identity and the better the maternal attachment was to the child, the higher levels of growth. Growth was also negatively related to endorsement of childbirth PTSD. Background factors, such as maternal age, education, and prior mental health, were associated with specific growth domains, although the association was small and there was no association with overall growth. Post-birth factors are important in ensuing psychological growth in the first months following birth. Attention to opportunities of growth following childbirth is warranted in clinical care, in particular following traumatic childbirth.

     

Retinal cone photoreceptor distribution in the American black bear (Ursus americanus)

The distribution of cone photoreceptor subtypes (important for color vision and vision quality) varies widely in different carnivore species, but there have been limited studies on bear (ursid) cone distribution. A previous behavioral study suggests that American black bears (Ursus americanus) are dichromatic, indicating that they possess two cone subtypes, although the retinal distribution of cones is unknown. The purpose of this study was to examine the subtype and topography of cones in American black bear retinas to further predict the nature of their color vision and image resolution. We studied 10 eyes from seven individual legally hunted black bears in northeastern North Carolina. Cryosections and retinal wholemounts were labeled using antibodies targeting two cone opsin subtypes: long/medium (L/M) wavelength sensitive and short (S) wavelength sensitive. Cones in fluorescent microscopy images were counted and density maps were created for retinal wholemounts. The black bear retina contains both cone subtypes and L/M cones outnumber S cones by at least 3:1, a finding confirmed in retinal frozen sections. There are higher concentrations of S cones present than typically seen in other carnivores with some evidence for co-expression of L/M and S cones. A cone-dense area centralis is present dorsotemporal to the optic nerve, similar to other carnivores. These results confirm that American black bears are predicted to have a dichromatic vision with high acuity indicated by the presence of a dorsotemporally located area centralis.     

Inflammation and fibrosis in chronic liver diseases including nonalcoholic fatty liver disease and hepatitis C

At present chronic liver disease(CLD),the third commonest cause of premature death in the United Kingdom is detected late,when interventions are ineffective,resulting in considerable morbidity and mortality.Injury to the liver,the largest solid organ in the body,leads to a cascade of inflammatory events.Chronic inflammation leads to the activation of hepatic stellate cells that undergo transdifferentiation to become myofibroblasts,the main extra-cellular matrix producing cells in the liver;over time increased extra-cellular matrix production results in the formation of liver fibrosis.Although fibrogenesis may be viewed as having evolved as a“wound healing”process that preserves tissue integrity,sustained chronic fibrosis can become pathogenic culminating in CLD,cirrhosis and its associated complications.As the reference standard for detecting liver fibrosis,liver biopsy,is invasive and has an associated morbidity,the diagnostic assessment of CLD by non-invasive testing is attractive.Accordingly,in this review the mechanisms by which liver inflammation and fibrosis develop in chronic liver diseases are explored to identify appropriate and meaningful diagnostic targets for clinical practice.Due to differing disease prevalence and treatment efficacy,disease specific diagnostic targets are required to optimally manage individual CLDs such as non-alcoholic fatty liver disease and chronic hepatitis C infection.To facilitate this,a review of the pathogenesis of both conditions is also conducted.Finally,the evidence for hepatic fibrosis regression and the mechanisms by which this occurs are discussed,including the current use of antifibrotic therapy.