Association of prenatal maternal perceived stress with a sexually dimorphic measure of cognition in 4.5-month-old infants.

Maternal prenatal stress can adversely impact subsequent child neurodevelopment, but little is known about its effect on cognitive development in infancy. This analysis of 107 infants from a prospective birth cohort assessed whether prenatal stress disrupts sexually dimorphic performance typically observed on a physical reasoning task. Maternal stress was assessed at 8-14 and 33-37 gestational weeks using the Perceived Stress Scale. Stress was defined as: low (scores below the median at both times), medium (scores above the median at one of the two times), and high (scores above the median at both times). At 4.5 months infants saw videos of two events: one impossible and the other possible. In the impossible event a box was placed against a wall without support underneath. In the possible event the box was placed against the wall, supported by the floor. Looking time at each event was recorded via infrared eye-tracking. Previous literature has shown that, at 4.5 months of age, girls typically look significantly longer at the impossible than at the possible event, suggesting that they expect the unsupported box to fall and are surprised when it does not. Boys tend to look equally at the two events suggesting that they do not share this expectation. This sex difference was replicated in the current study. General linear models stratified by sex and adjusted for household income, maternal education, mother's age at birth, infant's age at exam, and order of event presentation revealed that girls whose mothers reported high perceived stress during pregnancy had shorter looking time differences between the impossible and possible events than girls whose mothers reported low perceived stress (ß = -7.1; 95% CI: -12.0, -2.2 s; p = 0.006). Similar to boys, girls in the highest stress category spent about the same amount of time looking at each event. For boys, there were no significant looking time differences by maternal stress level. This finding suggests prenatal stress is associated with a delay in the development of physical reasoning in girls.

Shared and Study-specific Dietary Patterns and Head and Neck Cancer Risk in an International Consortium.

BACKGROUND: A few papers have considered reproducibility of a posteriori dietary patterns across populations, as well as pattern associations with head and neck cancer risk when multiple populations are available. METHODS: We used individual-level pooled data from seven case-control studies (3844 cases; 6824 controls) participating in the International Head and Neck Cancer Epidemiology consortium. We simultaneously derived shared and study-specific a posteriori patterns with a novel approach called multi-study factor analysis applied to 23 nutrients. We derived odds ratios (ORs) and 95% confidence intervals (CIs) for cancers of the oral cavity and pharynx combined, and larynx, from logistic regression models. RESULTS: We identified three shared patterns that were reproducible across studies (75% variance explained): the Antioxidant vitamins and fiber (OR = 0.57, 95% CI = 0.41, 0.78, highest versus lowest score quintile) and the Fats (OR = 0.80, 95% CI = 0.67, 0.95) patterns were inversely associated with oral and pharyngeal cancer risk. The Animal products and cereals (OR = 1.5, 95% CI = 1.1, 2.1) and the Fats (OR = 1.8, 95% CI = 1.4, 2.3) patterns were positively associated with laryngeal cancer risk, whereas a linear inverse trend in laryngeal cancer risk was evident for the Antioxidant vitamins and fiber pattern. We also identified four additional study-specific patterns, one for each of the four US studies examined. We named them all as Dairy products and breakfast cereals, and two were associated with oral and pharyngeal cancer risk. CONCLUSION: Multi-study factor analysis provides insight into pattern reproducibility and supports previous evidence on cross-country reproducibility of dietary patterns and on their association with head and neck cancer risk. See video abstract at, http://links.lww.com/EDE/B430.

Vitamin E intake from natural sources and head and neck cancer risk: a pooled analysis in the International Head and Neck Cancer Epidemiology consortium.

BACKGROUND: Evidence for the possible effect of vitamin E on head and neck cancers (HNCs) is limited. METHODS: We used individual-level pooled data from 10 case-control studies (5959 cases and 12 248 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium to assess the association between vitamin E intake from natural sources and cancer of the oral cavity/pharynx and larynx. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression models applied to quintile categories of non-alcohol energy-adjusted vitamin E intake. RESULTS: Intake of vitamin E was inversely related to oral/pharyngeal cancer (OR for the fifth vs the first quintile category=0.59, 95% CI: 0.49-0.71; P for trend <0.001) and to laryngeal cancer (OR=0.67, 95% CI: 0.54-0.83, P for trend <0.001). There was, however, appreciable heterogeneity of the estimated effect across studies for oral/pharyngeal cancer. Inverse associations were generally observed for the anatomical subsites of oral and pharyngeal cancer and within covariate strata for both sites. CONCLUSION: Our findings suggest that greater vitamin E intake from foods may lower HNC risk, although we were not able to explain the heterogeneity observed across studies or rule out certain sources of bias.

Early exposure to bisphenol A alters neuron and glia number in the rat prefrontal cortex of adult males, but not females.

Previous work has shown that exposure to bisphenol A (BPA) during early development can alter sexual differentiation of the brain in rodents, although few studies have examined effects on areas of the brain associated with cognition. The current study examined if developmental BPA exposure alters the total number of neurons and glia in the medial prefrontal cortex (mPFC) in adulthood. Pregnant Long-Evans rats were orally exposed to 0, 4, 40, or 400-µg/kg BPA in corn oil throughout pregnancy. From postnatal days 1 to 9, pups were given daily oral doses of oil or BPA, at doses corresponding to those given during gestation. Brains were examined in adulthood, and the volume of layers 2/3 and layers 5/6 of the mPFC was parcellated. The density of neurons and glia in these layers was quantified stereologically with the optical disector, and density was multiplied by volume for each animal. Males exposed to 400-µg/kg BPA were found to have increased numbers of neurons and glia in layers 5/6. Although there were no significant effects of BPA in layers 2/3, the pattern of increased neuron number in males exposed to 400-µg/kg BPA was similar to that seen in layers 5/6. No effects of BPA were seen in females or in males exposed to the other doses of BPA. This study indicates that males are more susceptible to the long-lasting effects of BPA on anatomy of the mPFC, an area implicated in neurological disorders.

Nutrient-based dietary patterns and the risk of head and neck cancer: a pooled analysis in the International Head and Neck Cancer Epidemiology consortium.

BACKGROUND: The association between dietary patterns and head and neck cancer has rarely been addressed. PATIENTS AND METHODS: We used individual-level pooled data from five case-control studies (2452 cases and 5013 controls) participating in the International Head and Neck Cancer Epidemiology consortium. A posteriori dietary patterns were identified through a principal component factor analysis carried out on 24 nutrients derived from study-specific food-frequency questionnaires. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using unconditional logistic regression models on quintiles of factor scores. RESULTS: We identified three major dietary patterns named 'animal products and cereals', 'antioxidant vitamins and fiber', and 'fats'. The 'antioxidant vitamins and fiber' pattern was inversely related to oral and pharyngeal cancer (OR=0.57, 95% CI 0.43-0.76 for the highest versus the lowest score quintile). The 'animal products and cereals' pattern was positively associated with laryngeal cancer (OR=1.54, 95% CI 1.12-2.11), whereas the 'fats' pattern was inversely associated with oral and pharyngeal cancer (OR=0.78, 95% CI 0.63-0.97) and positively associated with laryngeal cancer (OR=1.69, 95% CI 1.22-2.34). CONCLUSIONS: These findings suggest that diets rich in animal products, cereals, and fats are positively related to laryngeal cancer, and those rich in fruit and vegetables inversely related to oral and pharyngeal cancer.

Native fluorescence spectroscopic evaluation of chemotherapeutic effects on malignant cells using nonnegative matrix factorization analysis.

The native fluorescence spectra of retinoic acid (RA)-treated and untreated human breast cancerous cells excited with the selective wavelengths of 300 nm and 340 nm were measured and analyzed using a blind source separation method namely Nonnegative Matrix Factorization (NMF). The results show that the fluorophores of human malignant breast cells change their compositions when they are treated with RA. The reduced contribution from tryptophan, NADH and flavin to the fluorescence of the treated breast cancerous cells was observed in comparison with that of the untreated cells. The results indicate that the decrease of adenosine triphosphate (ATP) in the RA-treated cells. The possible clinical applications of this native fluorescence study are discussed.

New processing technique for viscous amorphous materials and characterisation of their stickiness and deformability.

This paper reports on a technique using ultrasound-assisted equipment to characterise and handle stickiness of viscous amorphous blends of citric acid and paracetamol after melt mixing and during processing. Deformability and stickiness were studied using a specially designed sample measurement compartment. An ultrasound-assisted nozzle and knife for pharmaceutical applications were studied. The application of ultrasound was found to increase the mass flow through a nozzle connected to a pressurized tank. This effect was found to be separate from the increased mass transport resulting from the reduced viscosity as the temperature was increased. Ultrasound was also found to have a favourable influence on cutting through melt extrudates. The stickiness and resistance to deformation of samples were observed to be dependent on the amount of paracetamol in the blend and temperature that was in agreement with the glass transition temperature and viscosity. Other influencing factors, such as time-dependent wetting and surface energetics, are discussed. We conclude that it is possible to characterise stickiness and resistance to deformation of viscous amorphous materials with a specially designed probe test, and the stickiness of amorphous material can be handled during processing with ultrasound-assisted equipment.

Characterization of ultrasound extrudated and cut citric acid/paracetamol blends.

The purpose of the present work was to study the effect of ultrasound extrusion and cutting on the physical stability of a viscous and sticky supercooled melt containing (50/50, w/w, %) citric acid anhydrate and paracetamol. Samples were extrudated at temperatures of 50, 60, and 70 degrees C using power levels of 0, 50, 100, and 150 W. Similarly, extrudates prepared at 60 degrees C were cut at temperatures ranging from 25-60 degrees C with an ultrasound knife in the range 0, 50, and 100 W. The characterization methods used were: high performance liquid chromatography, differential scanning calorimetry, Karl Fischer titration, X-ray powder diffraction, Fourier transform infrared microscopy, optical- and stereomicroscopy. There was no physical difference in extrudates or cut surfaces whether processed with or without ultrasound. During 1-year aging time in dry conditions, all the samples were observed to crystallize slowly and ultrasound processing did not enhance the crystallization. Ultrasound thus holds some promise for processing of viscous and sticky pharmaceuticals, provided the material is physically stable enough to withstand mechanical and thermal stress. Processing of sticky and viscous material would be difficult without ultrasound with the methods currently used in pharmaceutical industry.

A solid-state NMR study of phase structure, molecular interactions, and mobility in blends of citric acid and paracetamol.

Citric acid anhydrate (CAA) and paracetamol (PARA), prepared as crystalline physical mixtures and as amorphous blends, were studied using (13)C solid-state cross polarization magic angle spinning (CPMAS) NMR. Amorphous blends showed significant line broadening from the conformational distribution as compared to the crystalline samples. Also, chemical shift variations were observed between crystalline and amorphous blends, which were attributed to differences in intermolecular interactions. Averaging of proton rotating-frame spin-lattice relaxation times (T(1rho)) probed via different (13)C sites in the amorphous blends confirmed molecular level mixing. For some, initially amorphous, sample compositions the onset of crystallization was evident directly from spectra and from the significantly longer T(1rho) relaxations. Thus, crystallization caused phase separation with properties of the two phases resembling those of pure CAA and PARA, respectively. (13)C spectra of amorphous 50/50 (w/w, %) CAA/PARA recorded from above the glass transition temperature broadened as the temperature increased to a maximum at T approximately T(g) + 33 K. This was the result of a dynamic interference between the line narrowing techniques being applied and the time scale of molecular reorientation in the miscible melt. The derived average correlation time was found to correspond well with previous results from melt rheology. We conclude that the underlying reasons for physical instability (i.e., crystallization from the miscible melt, including molecular interactions and dynamics) of this class of amorphous binary mixtures can be effectively evaluated using NMR spectroscopy.

Pilot study using SELDI-TOF-MS based proteomic profile for the identification of diagnostic biomarkers of thyroid proliferative diseases.

Biomarkers for thyroid cancer (TCa) lack specificity. To develop TCa specific biomarkers, SELDI-TOF-MS was used to examine the proteomic profile of biopsies obtained from papillary TCa along with adjacent normal tissue. Sixty-three potential biomarkers were categorized by univariate analysis into single biomarker candidates and segregated by multivariate analysis into normal and cancerous groups. Our studies demonstrate the sensitivity and reproducibility of this approach to detect biomarkers for TCa.

A simple method for fixation and microdissection of frozen fresh tissue sections for molecular cytogenetic analysis of cancers.

Microdissection has been widely used for procuring DNA from specific microscopic regions of formalin fixed, paraffin embedded tissue sections. We have developed a method for fixation and microdissection of frozen fresh biopsy tissue sections. Five micrometer frozen fresh tissue sections were fixed with ethanol and stored at room temperature. Well defined regions from hematoxylin and eosin (H & E) stained or unstained sections were briefly steamed and microdissected using a needle. The dissected tissue was digested with proteinase K and DNA was isolated. Whole genome amplifications were obtained by degenerate oligonucleotide primed polymerase chain reaction (DOP-PCR) from these samples. The reliability of this technique was demonstrated by comparing conventional comparative genomic hybridization (CGH) with DOP-PCR-CGH. The advantages of this method are that frozen fresh sections can be fixed easily and stored for more than 4 years, it is easy to microdissect and pick-up very minute regions (0.1 mm(2)), and it is rapid; microdissection and purification can be accomplished within 3 h. Using DNA from microdissected sections, DOP-PCR-CGH revealed genetic abnormalities more accurately than conventional CGH. Although this novel method was demonstrated using DOP-PCR-CGH, we believe that it will be useful for other genetic analyses of specific small regions and cell populations. We also observed whether storage time, H & E staining and crude DNA extracts affected the quality of amplified DNA. DNA integrity was maintained for at least 49 months in ethanol fixed sections that were stored at room temperature, but DNA was gradually degraded after one month if the ethanol fixed sections had been H & E stained and stored. When crude DNA extracts from H & E stained sections were used, the size of the DOP-PCR product was reduced. Our study suggests that ethanol fixed tissue sections may be stored at room temperature for at least 4 years without DNA degradation, the H & E stains may not affect the quality of amplified DNA, but H & E or other components in the staining process may reduce the size of DOP-PCR product, which is critical for the quality of CGH hybridization.

Tetrachlorodibenzo-p-dioxin exposure alters radial arm maze performance and hippocampal morphology in female AhR mice.

Perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been reported to alter spatial learning in rats tested on a radial arm maze (RAM). TCDD is believed to exert most of its effects through binding to the aryl hydrocarbon receptor (AhR). To determine whether the AhR mediates TCDD-induced alterations in spatial learning, we tested male and female AhR-knockout (AhR-/-), heterozygous (AhR+/-) and wild-type (AhR+/+) mice on the RAM. AhR+/- male and female mice were time mated, and treated dams were dosed with 5 microg TCDD/kg body weight on day 13 of gestation. When offspring reached adulthood, male and female AhR+/+, AhR+/- and AhR-/- mice from TCDD-exposed and unexposed litters were tested on the eight-arm RAM. After testing, we examined hippocampal morphology as visualized by the Timm's silver sulfide stain. TCDD-exposed female AhR+/- mice made more errors than their respective controls on the RAM and exhibited a decrease in the size of the intra- and infrapyramidal mossy fiber (IIP-MF) field of the hippocampus. None of the other TCDD-exposed groups differed from their respective control groups with regard to maze performance or hippocampal morphology. The reduction of IIP-MF field indicates a possible morphological basis for the learning deficit that was observed in the female AhR+/- mice. It is hypothesized that the effect of TCDD exposure is AhR dependent and that TCDD may alter GABAergic activity in the hippocampus of female mice during development.

Cognitive effects of endocrine-disrupting chemicals in animals.

A large number of chemical pollutants including phthalates, alkylphenolic compounds, polychlorinated biphenyls and polychlorinated dibenzodioxins, organochlorine pesticides, bisphenol A, and metals including lead, mercury, and cadmium have the ability to disrupt endocrine function in animals. Some of these same chemicals have been shown to alter cognitive function in animals and humans. Because hormonally mediated events play a central role in central nervous system development and function, a number of researchers have speculated that the changes in cognitive function are mediated by the endocrine-like actions of these chemicals. In this paper we review the evidence that cognitive effects of chemicals classified as environmental endocrine disruptors are mediated by changes in hormonal function. We begin by briefly reviewing the role of gonadal steroids, thyroid hormones, and glucocorticoids in brain development and brain function. We then review the endocrine changes and cognitive effects that have been reported for selected endocrine-disrupting chemicals, discuss the evidence for causal relationships between endocrine disruption and cognitive effects, and suggest directions for future research.

Tobacco carcinogen-detoxifying enzyme UGT1A7 and its association with orolaryngeal cancer risk.

BACKGROUND: UDP-glucuronosyltransferase 1A7 (UGT1A7) detoxifies several tobacco carcinogens. We determined whether UGT1A7 expression is observed in normal orolaryngeal tissue and whether UGT1A7 allelic variations are associated with the risk for orolaryngeal cancer. METHODS: UGT1A7 expression in normal orolaryngeal tissue was determined by semiquantitative reverse transcription-polymerase chain reaction (PCR). Buccal cell DNA isolated from 194 case subjects with orolaryngeal cancer and from 388 control subjects who were matched by sex, age, and race was subjected to UGT1A7 genotyping with the use of combined PCR-restriction fragment length polymorphism and allelic discrimination analysis. All statistical tests were two-sided. RESULTS: UGT1A7 messenger RNA was expressed at similar levels in the esophagus, tongue, tonsil, floor of the mouth, and larynx. Genotyping revealed the presence of three variant reduced-activity UGT1A7 alleles in both Caucasians and African-Americans. Individuals with any of the predicted low-activity UGT1A7 genotypes had an increased risk of orolaryngeal cancer (odds ratio [OR] = 3.7; 95% confidence interval [CI] = 1.7 to 8.7) relative to subjects with the wild-type genotype. Both Caucasians and African-Americans with the low-activity genotypes had statistically significantly increased orolaryngeal cancer risk compared with Caucasians and African-Americans with the wild-type genotype (OR = 2.8 [95% CI = 1.1 to 7.6] and OR = 6.2 [95% CI = 1.2 to 31], respectively). For subjects with the predicted low-activity genotypes, the risks of oral cavity cancer (OR = 4.2; 95% CI = 1.7 to 10) and laryngeal cancer (OR = 3.7; 95% CI = 0.99 to 14) were similar. There was no association between UGT1A7 genotype and orolaryngeal cancer risk in never smokers, whereas subjects with predicted low-activity UGT1A7 genotypes who were light smokers (OR = 3.7; 95% CI = 1.1 to 12) or heavy smokers (OR = 6.1; 95% CI = 1.5 to 25) had an increased risk. CONCLUSIONS: The tissue expression of UGT1A7 is consistent with the possibility of a physiologic role in orolaryngeal cancer. Variations in the UGT1A7 gene that reduce UGT1A7 activity may affect the risk of smoking-related orolaryngeal cancer.

Impairments of memory and learning in older adults exposed to polychlorinated biphenyls via consumption of Great Lakes fish.

An association between in utero polychlorinated biphenyl (PCB) exposure and impaired childhood intellectual functioning has been reported, but the potential impact of PCB exposure during adulthood on intellectual functioning has received little attention. We assessed the impact of PCBs and other fish-borne contaminants on intellectual functioning in older adults. The subjects were 49- to 86-year-old Michigan residents recruited from an existing cohort. Fish eaters ate > 24 lb of sport-caught Lake Michigan fish per year and non-fish eaters ate < 6 lb of Lake Michigan fish per year. A battery of cognitive tests including tests of memory and learning, executive function, and visual-spatial function was administered to 180 subjects (101 fish eaters and 79 non-fish eaters). Blood samples were analyzed for PCBs and 10 other contaminants. We evaluated cognitive outcomes using multiple regression. PCBs and dichlorodiphenyl dichloroethene (DDE) were markedly elevated in fish eaters. After controlling for potential confounders PCB, but not DDE, exposure was associated with lower scores on several measures of memory and learning. These included the Weschler Memory Scale verbal delayed recall (p = 0.001), the semantic cluster ratio (p = 0.006), and list A, trial 1 (p = 0.037), from the California Verbal Learning Test. In contrast, executive and visual-spatial function were not impaired by exposure to either PCBs or DDE. In conclusion, PCB exposure during adulthood was associated with impairments in memory and learning, whereas executive and visual-spatial function were unaffected. These results are consistent with previous research showing an association between in utero PCB exposure and impairments of memory during infancy and childhood.

Spatial reversal learning in Aroclor 1254-exposed rats: sex-specific deficits in associative ability and inhibitory control.

Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants that have been associated with cognitive deficits in children exposed in utero. Cognitive deficits due to PCB exposure have also been documented in animal models, but the underlying behavioral mechanisms responsible for those deficits remain to be elucidated. The current study examined the effects of gestational and lactational exposure to PCBs on spatial discrimination-reversal learning (spatial RL) in rats using standard two-lever operant testing chambers. Pregnant Long-Evans rats (10/dose) received either 0 or 6 mg/kg Aroclor 1254 (A1254) po in corn oil from gestational day 6 to postnatal day 21. One male and one female from each litter were tested on spatial RL beginning at 190-220 days of age. Animals were reinforced with a 45-mg food pellet for pressing the lever associated with the correct spatial location (either left or right). After reaching 85% correct performance for 2 consecutive days, the opposite spatial location was reinforced. Five of these position reversals were given. Male rats exposed to A1254 made significantly more total errors (121.6 +/- 12.5) on the first reversal than controls (90.7 +/- 5.8). In contrast, female rats exposed to A1254 exhibited deficits on the fourth and fifth reversals (23.6 +/- 4.2, 17.0 +/- 2.8 and 36.7 +/- 4.7, 26.8 +/- 2.5 for control and exposed animals, respectively). Response-pattern analyses in the A1254-exposed male and female rats revealed fundamental differences in the underlying behavioral mechanisms responsible for the deficits. A1254-exposed males exhibited an increased tendency to incorrectly respond to the previously correct stimulus (i.e., perseverate) following a reversal while A1254-exposed females exhibited impairments in their ability to make new associations with a reinforced spatial location (i.e., associative deficit). These data provide new insights into the underlying behavioral mechanisms that may be responsible for the spatial learning deficits observed in PCB-exposed rodents and monkeys.

Elucidation of CYP2E1 5' regulatory RsaI/Pstl allelic variants and their role in risk for oral cancer.

The CYP2E1 gene, whose protein product plays an important role in the metabolism of various carcinogens, exhibits two polymorphisms recognized by the restriction enzymes RsaI and PstI in its transcriptional regulatory region that have been previously implicated in cancer susceptibility. In this study, we have examined these polymorphisms to elucidate CYP2E1 allelic haplotype, examining the prevalence of these CYP2E1 alleles in Caucasians and African Americans and their potential role in risk for oral cancer. In addition to the c1 (RsaI[+]/PstI[-]) and c2 (RsaI[-]/PstI[+]) alleles reported in previous studies, we have identified two new alleles, c3 (RsaI[+]/PstI[+]) and c4 (RsaI[-]/PstI[-]). The prevalence of the c2 and c3 alleles differs between racial groups, with African Americans exhibiting a lower prevalence of the c2 allele (0.003) but a higher prevalence of the c3 allele (0.049) than Caucasians (0.031 for c2 and 0.004 for c3). Of the 570 subjects screened in this study, the c4 allele was observed in one subject, a Caucasian case with the (c4/c4) genotype. A significant increase in the CYP2E1 (c1/c1) genotype was observed in oral cancer cases as compared to frequency-matched controls in subjects who smoked < or =24 pack-years (P=0.033). No association was observed between CYP2E1 genotype and risk for oral cancer in the heavy-smoking group (i.e. > 24 pack-years). Similar trends were observed for both Caucasians and African Americans. These data suggest that the c1 allele may contribute to increased risk for oral cancer.

Estrogen metabolism as a risk factor for head and neck cancer.

OBJECTIVE: Estrogen metabolites have been associated in the pathogenesis of breast and cervical cancer; 16alpha-hydroxyestrone(16alpha-OHE1) demonstrated proliferative effects whereas 2-hydroxyestrone(2-OHE1) had antiproliferative effects. Our study's objective is to demonstrate that head and neck (H&N) cancer patients metabolize estrogen differently than healthy controls, which may constitute a risk factor for H&N cancer development. STUDY DESIGN: Urinary metabolite levels of 2-OHE1 and 16alpha-OHE1 from 50 H&N cancer patients and 50 age- and sex-matched controls were measured using enzyme-linked immunosorbent assay (ELISA). Absolute values and 2-/16alpha-OHE1 ratios were calculated. Conditional logistic regression for univariate and multivariate analysis with odds ratio (OR) and 95% confidence interval (CI) were used. RESULTS: Thirty percent (15 of 50) from the case group had a low 2-/16alpha-OHE1 ratio compared with only 4% (2 of 50) in the control group (OR = 11.1; 1.4-91.5, 95% CI) (P < 0.05). When adjusted for tobacco, OR remained significant at 15.6 (1.1-212.5, 95% CI) (P < 0.05). CONCLUSION: H&N cancer patients are more likely to express abnormal estrogen metabolism than healthy controls; 2-/16alpha-OHE1 may serve as a potential biological marker of individuals at increased risk of H&N cancer.

Parotid and thyroid gland cancers in patients with ataxia-telangiectasia.

This study describes the clinicopathologic features of parotid and thyroid gland cancers in patients with ataxia-telangiectasia (AT). The medical records of 412 AT patients were reviewed to identify those patients who developed parotid or thyroid gland cancers. Presenting features, diagnoses, types of therapy, risk factors, and other primary cancers were analyzed. Five patients with parotid or thyroid gland cancers were identified. Three had parotid (2 mucoepidermoid and 1 acinic cell) and 2 had thyroid gland (1 papillary and 1 follicular) cancers. Four patients presented with head and neck masses and 1 had an occult papillary thyroid carcinoma. Four patients had more than one primary cancer. The only mode of therapy was surgery. The 2 patients with mucoepidermoid carcinoma had complete parotidectomies. One is alive without any evidence of disease 12 months after diagnosis and 1 died of refractory lymphoma without any evidence of mucoepidermoid carcinoma at autopsy. The patient with acinic cell carcinoma had a parotid biopsy only. The 2 patients with thyroid cancer were diagnosed at autopsy. The results indicate that patients with AT are at risk for developing multiple primary cancers including those of the parotid and thyroid gland, and should be evaluated for such primaries.

Gestational and lactational exposure to TCDD or coplanar PCBs alters adult expression of saccharin preference behavior in female rats.

Previous studies have shown that maternal doses of 1 microg/kg or less of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in late gestation can demasculinize and feminize reproductive behavior in male rats. However, it was not known whether coplanar polychlorinated biphenyls (PCBs) had similar effects, or whether non-reproductive sexually dimorphic behaviors such as saccharin preference behavior were also altered. We determined the effects of TCDD or coplanar PCBs on saccharin consumption and saccharin preference in male and female rats. Sprague-Dawley rats were dosed with 3,3',4, 4'-tetrachlorobiphenyl (PCB 77; 2 or 8 mg/kg/day), 3,3',4,4', 5-pentachlorobiphenyl (PCB 126; 0.25 or 1.0 microg/kg/day), TCDD (0. 025 or 0.10 microg/kg/day), or corn oil vehicle on days 10-16 of gestation. Maternal exposure to TCDD or coplanar PCBs did not change saccharin consumption or saccharin preference in male rats. However, TCDD and coplanar PCB-exposed females showed decreased saccharin consumption and saccharin preference. The results indicate that saccharin consumption is masculinized in female rats exposed to TCDD or coplanar PCBs during perinatal development. This effect could be related to the anti-estrogenic actions of these chemicals.