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.     

Correlations between skeletal muscle mass and bone mass in children 6-18 years: influences of sex, ethnicity, and pubertal status

A constant sex-specific relationship between skeletal muscle mass and bone mass was observed in healthy adults based on TBK/TBCa, using TBK (total body potassium) by 40K counting and TBCa (total body calcium) by in-vivo neutron activation analysis (Ellis and Cohn, 1975). We revisited this topic in children by studying correlations between TBK and TBCa, and by comparing TBK/TBCa between sexes, pubertal groups (prepubertal and pubertal) and ethnic groups in 141 white, 101 black, and 62 Asian healthy children, aged 6 - 18 years, living in New York City. TBK was measured by 40K counting, and TBCa by dual energy x-ray absorptiometry. TBK and TBCa were significantly correlated from 6 to 18 years (r > 0.93), but the correlation equations varied by gender and ethnicity. Boys had significantly more TBK and greater TBK/TBCa than girls at a given age and weight, reflecting greater skeletal muscle mass in boys from 6 years, the age at which the study started. TBK/TBCa in blacks was significantly smaller than whites and Asians in both sexes in prepuberty and puberty, and pubertal black girls had the smallest mean TBK/TBCa. No significant differences were found between whites and Asians. TBK/TBCa decreased as body weight increased in prepubertal girls, and decreased as body weight and age increased in pubertal girls, but did not change with body weight or age in boys of any subgroup. The inverse relationship between TBK/TBCa and age in pubertal girls suggests greater increase in TBCa compared to TBK than in other groups, while the constant TBK/TBCa in boys reflects proportional increases in TBK and TBCa. Thus TBK/TBCa can be used as an index of relative growth in skeletal muscle mass and bone mass in white, black, and Asian children according to sex, age and pubertal status.     

Opiate induced feeding is not dependent on the hippocampus

It has been shown that spreading depression of the hippocampus can elicit feeding, and that several opioid peptides elicit spreading depression when injected into the hippocampus. To determine whether such depression is the primary mechanism by which opiates induce feeding, we tested the feeding effects of naloxone, an opiate antagonist, and butorphanol tartrate, a kappa-sigma agonist, on feeding in rats with and without hippocampal lesions. Naloxone tended to reduce intake approximately equally in the two groups. Similarly, the doses of butorphanol that increased intake in sham rats were equally effective in lesioned rats. It was concluded that the hippocampus is not the major structure mediating opiate-induced feeding.     

Correlates of Control in Pediatric Cancer Patients and Their Families

Physical illness is a life experience which challenges an individual'ssense of control and thus represents a potential threat to mentalhealth. For children, a serious illness threatens not only theirsense of physical and psychological well-being but also threatensthe psychological well-being of their family. In this study,severely ill patients (n = 15) and a member of their family(n = 15) were interviewed. The patients, who ranged in age from12 to 21 years, were being treated for metastatic solid tumorsor lymphoma that failed to respond to conventional therapeuticregimens. Correlates of control for the patients and familymembers, the relationship between control and developmentalstage of the patients, and the difference between levels ofcontrol in patients and family member were examined. The findingsare discussed in relation to development and their implicationsfor medical management.     

Social status constrains the stress response in the squirrel monkey.

The influence of dominance on the pituitary-adrenal and gonadal systems was evaluated in male squirrel monkeys. Basal and stress levels of plasma cortisol and testosterone were determined in eight male pairs across a 5-week period. The data indicated that squirrel monkeys have unusually high levels of steroid hormones in comparison to other species. Dominant males had higher levels of cortisol and testosterone and showed a smaller stress response than did subordinate males.     

Cholera.

Despite more than a century of study, cholera still presents challenges and surprises to us. Throughout most of the 20th century, cholera was caused by Vibrio cholerae of the O1 serogroup and the disease was largely confined to Asia and Africa. However, the last decade of the 20th century has witnessed two major developments in the history of this disease. In 1991, a massive outbreak of cholera started in South America, the one continent previously untouched by cholera in this century. In 1992, an apparently new pandemic caused by a previously unknown serogroup of V. cholerae (O139) began in India and Bangladesh. The O139 epidemic has been occurring in populations assumed to be largely immune to V. cholerae O1 and has rapidly spread to many countries including the United States. In this review, we discuss all aspects of cholera, including the clinical microbiology, epidemiology, pathogenesis, and clinical features of the disease. Special attention will be paid to the extraordinary advances that have been made in recent years in unravelling the molecular pathogenesis of this infection and in the development of new generations of vaccines to prevent it.     

Human submandibular-sublingual saliva promotes adhesion of Candida albicans to polymethylmethacrylate.

The purpose of this study was to identify components of saliva that interact with Candida albicans in solution and that may modulate adhesion to dental acrylic (polymethylmethacrylate [PMMA]) surfaces. Saliva-derived pellicles extracted from C. albicans blastoconidia and hyphal-form cells mixed with fresh human submandibular-sublingual saliva (HSMSL) contained predominantly high- and low-molecular-weight mucins (MG1 and MG2, respectively). In contrast, few components from fresh human parotid saliva were adsorbed to yeast cells. Coating PMMA beads with HSMSL significantly enhanced (10-fold) adhesion of both growth forms of C. albicans compared with human parotid saliva (2-fold), suggesting a role for mucins in adhesion. HSMSL-enhanced adhesion was completely abolished by preadsorbing HSMSL with either blastoconidia or hyphal-form cells prior to coating PMMA. However, coating PMMA with purified salivary mucins or the addition of mucin to preadsorbed saliva did not enhance or restore adhesion to levels found with fresh HSMSL. Adhesion assays employing guanidine-treated fresh HSMSL showed a complete lack of Candida binding, suggesting that subjecting HSMSL to dissociating conditions may alter a property of salivary mucins crucial for C. albicans adhesion. Protease and glycosidase treatment of yeast cells significantly reduced adhesion to HSMSL-coated PMMA. In addition, preincubation of C. albicans with mannose and galactose inhibited adhesion to HSMSL-coated PMMA. These results suggest that mucins may play a role in C. albicans adhesion to saliva-coated PMMA and that a glycoprotein on the yeast surface may be involved in these events.     

Usefulness of an enzyme-linked immunosorbent assay for detection of Giardia antigen in feces.

The usefulness of a recently developed enzyme-linked immunosorbent assay which detects Giardia lamblia antigen in feces was determined in experimentally infected humans. Giardia antigen was determined in serially collected fecal specimens from humans inoculated with two Giardia isolates, GS/M and Isr. A total of 277 stools from 18 volunteers were tested, 74 from Isr-inoculated volunteers and 203 from GS/M-inoculated volunteers. None of the five Isr-inoculated volunteers became infected, and none of their stools contained Giardia antigen. In contrast, all of the 13 GS/M-inoculated volunteers became infected, and Giardia antigen was present one or more times in the stools of each. Of 203 stools from GS/M-inoculated volunteers, 73 contained Giardia cysts, and 69 of these (94.5%) had detectable antigen. In contrast, 108 of the 203 specimens were positive for Giardia antigen and only 73 had cysts. Most antigen-positive but cyst-negative specimens occurred during treatment, but during patency 71 stools contained antigen and 65 had cysts. The enzyme-linked immunosorbent assay is infections and is easier to perform.