Evidence for the involvement of proximal chromosome 3P loci in the progression of Von Hippel-Lindau related tumors

Von Hippel-Lindau (VHL) disease is an autosomal dominant disorder characterized by the development of retinal and central nervous system hemangioblastoma, renal cell carcinoma (RCC), pheochromocytoma and pancreatic islet cell tumors (PICT). The VHL gene maps to chromosome 3p25 and has been shown to be mutated in 57% of sporadic cases of RCC, implicating VHL in the genesis of RCC. We report a multigeneration VHL kindred in which four affected female siblings developed PICT at early ages. Analysis of the three coding exons of the VHL gene in this family revealed a single, missense mutation in codon 238. Inheritance of the 238 mutation has been reported to correlate with a 62% risk of pheochromocytoma development. In this kindred, all affected individuals carried the mutation as well as one additional sibling who showed no evidence of disease. Clinical screening of this individual indicated small ($<$1 cm) pancreatic and kidney tumors. Results suggest that inheritance of the codon 238 mutation does not correlate with early onset pheochromocytoma. Rather, the only individual in the pedigree with pheochromocytoma was the proband's mother who developed bilateral pheochromocytoma at the age of 62. Thus, the VHL codon 238 mutation may predispose to late onset pheochromocytoma in this family; however, it does not explain the preponderance of PICT in the third generation since this mutation has not been reported to increase the risk of developing pancreatic lesions. This suggests that inheritance of the codon 238 mutation and subsequent somatic inactivation of the wild type allele of the VHL gene may not be sufficient to explain the initiation and subsequent progression to malignancy in VHL-associated neoplasms. Since the two tumor types that most frequently progress to malignancy are RCC and PICT, we asked whether loss of heterozygosity (LOH) could be detected proximal to the VHL gene on chromosome 3 in distinct regions of 3p previously implicated by LOH and cytogenetic studies to contain tumor suppressor loci for RCC. LOH was performed on high molecular weight DNA isolated from peripheral blood and frozen tumor tissue of family members using microsatellite markers spanning 3p. Results indicated LOH for all informative 3p loci in tumor tissue from affected individuals with PICT. LOH was detected along the entire length of the chromosome arm and included the proximal region of 3p13-14.2 implicated in the hereditary form of renal cell carcinoma.^ If 3p LOH were a critical event in pancreatic islet cell tumorigenesis, then it should be expected that LOH in sporadic islet cell tumors would also be observed. We expanded LOH studies to include sporadic cases of PICT. Consistent LOH was observed on 3p with a highest frequency LOH in the region 3p21.2. This is the first evidence for an association between chromosome 3 loci and pancreatic islet cell tumorigenesis. (Abstract shortened by UMI.) ^

Ethnic differences in food availability at home among 3--5 year old preschoolers attending Head Start centers in 2008

Background. The childhood obesity epidemic has disproportionately impacted the lives of low-income, minority preschoolers and their families. Research shows that parents play a major role as "gatekeepers" who control what food is brought into the home and as role models for dietary practices. Currently, there is limited research regarding ethnic differences in families of low-income preschoolers. ^ Objective. The objective of this study was to look at ethnic differences in food availability at home among the low-income families of Hispanic and African American preschoolers attending Head Start centers in Harris County, Texas. ^ Design/Subjects. Descriptive data on food availability at home between Hispanic and African American families were used and analyzed for this study. Parents or primary caregivers (n = 718) of children enrolled at Head Start Centers in Houston, Texas completed the Healthy Home Survey. ^ Methods. In the Healthy Home Survey, participants were asked to answer open-ended questions regarding various types of foods currently available at home, such as fresh, canned or jarred, dried and frozen fruits; fresh, canned or jarred, and frozen vegetables; salty snacks, sweet snacks, candy, and soda. Descriptive analyses were conducted to identify significant differences between Hispanics and African Americans via a paired t-test to compare the means of variables between the study groups and a Pearson's chi-square or Fischer's exact (if cell size was <5) test calculated for food availability (food types) between ethnicities to determine differences in distributions. ^ Results. Although both Hispanics and African Americans reported having all categories of food types at home, there were statistically significant differences between ethnic groups. Hispanics were more likely to have fresh fruits and vegetables at home than African Americans. At the same time, more African American families reported having canned or jarred fruits and canned green/leafy vegetables than Hispanics. More Hispanic families reported having diet, regular, and both diet and regular sodas available compared to African American families. However, high percentages of unhealthy foods (including snacks and candy) were reported by both ethnicities. ^ Conclusions. The findings presented in this study indicate the implicit ethnic differences that exist in the food availability among low-income families of Hispanic and African American preschoolers. Future research should investigate the associations between food availability and children's weight status by ethnicity to identify additional differences that may exist.^

Emergency department usage patterns among residents of Hardin, Jefferson, and Orange Counties in southeast Texas

Emergency departments (EDs) have been called the net below the safety net due to their long history of providing care to the uninsured and others lacking access to the healthcare system. In past years, those with Medicaid and, more recently, those with Medicare, are also utilizing the ED as a medical home for routine primary care. There are many reasons for this but the costs to the community have become increasingly burdensome. ^ To evaluate how often the ED is being utilized for primary care, we applied a standardized tool, the New York University Algorithm, to over 43,000 ED visits when no hospitalization was required made by Hardin, Jefferson, and Orange County residents over a 12 month period. We compared our results to Harris County, where studies using the same framework have been performed, and found that sizeable segments of the population in both areas are utilizing the ED for non-emergent primary care that could be treated in a more cost-effective community setting. ^ We also analyzed our dataset for visit-specific characteristics. We found evidence of two possible health care disparities: (1) Blacks had a higher rate of primary care-related ED visits in relation to their percentage of the population when compared to other racial/ethnic groups; and (2) when form of payment is considered, the uninsured were more likely to have a primary care-related ED visit than any other group. These findings suggest a lack of community-based primary care services for the medically needy in Southeast Texas. ^ We believe that studies such as this are warranted elsewhere in Texas as well. We plan to present our findings to local policy makers, who should find this information helpful in identifying gaps in the safety net and assist them in better allocating scarce community resources. ^

Food availability in the home and dietary intake of the Harris County Department of Education Head Start population

Background. The prevalence of obesity and overweight children has been an ongoing health epidemic in the US for the last several decades. The problem has consistently worsened and has disproportionately been the most prevalent among low socioeconomic status (SES) populations. Food availability in the home has been suggested to be a potential factor related to overweight and obesity, as availability is likely associated with intake. Food availability of low SES preschool aged children has not been well examined. The purpose of this study was to explore the food environment of the Harris County Department of Education (HCDE) Head Start population, and describe reported frequency of intake of particular food groups. The effect of food availability on reported intake was also examined.^ Methods. This was a cross-sectional study of secondary data analysis. Data obtained from 17 HCDE Head Start Centers was analyzed using PASW 18 Statistical Software. Demographic analyses included population, age, gender, race, parent occupation, type of home, and language spoken in the home. Descriptive statistics included reported availability of foods in the home as well as frequency of intake.^ Regression analysis examined the relationship of availability of foods on intake. The food categories included were: dark leafy green and orange vegetables, other vegetables, fruits, soda, salty snacks, and sweet snacks. For both vegetable categories reported intake of fresh, frozen, and canned vegetables were included. For the fruit category, intake of fresh, frozen, canned, and dried fruits were reported.^ Results. Results showed that 90-95% of parents reported having vegetables and fruits available in the home. However, the only significant relationship between availability and intake was for fresh fruit and dried fruit. No associations were seen among the vegetable groups. Other vegetables (bell peppers, eggplant, tomatoes, onions, iceberg lettuce, asparagus) that were frozen, approached significance for availability on intake, however once adjusted for confounders the relationship was no longer present. Among soda, salty snacks, and sweet snacks the only significant relationship was seen for soda availability and intake. Salty snacks and sweet snacks presence in the home was not a predictor of increased frequency of intake.^ Conclusions. This research supported the hypothesis that availability of foods has an impact on intake for fresh fruits, dried fruits and soda. No associations were seen for vegetables, salty snacks and sweet snacks. Additionally, most of the parents reported having fruits and vegetables in the home, but reported intakes were not meeting the Dietary Guidelines for Americans recommendations. Strengths of the study included the large sample size taken from numerous HCDE Head Start Centers. Limitations included questionable reliability of participant’s responses, ability to generalize to other populations, and the use of secondary data rather than prospectively collected data.^

Intercellular adhesion and membrane polarity in rat hepatocytes: Localization of cell -CAM 105 and other domain-specific membrane proteins {\it in situ\/} and {\it in vitro\/} by electron microscopy

Cell-CAM 105 has been identified as a cell adhesion molecule (CAM) based on the ability of monospecific and monovalent anti-cell-CAM 105 antibodies to inhibit the reaggregation of rat hepatocytes. Although one would expect to find CAMs concentrated in the lateral membrane domain where adhesive interactions predominate, immunofluorescence analysis of rat liver frozen sections revealed that cell-CAM 105 was present exclusively in the bile canalicular (BC) domain of the hepatocyte. To more precisely define the in situ localization of cell-CAM 105, immunoperoxidase and electron microscopy were used to analyze intact and mechanically dissociated fixed liver tissue. Results indicate that although cell-CAM 105 is apparently restricted to the BC domain in situ, it can be detected in the pericanalicular region of the lateral membranes when accessibility to lateral membranes is provided by mechanical dissociation. In contrast, when hepatocytes were labeled following incubation in vitro under conditions used during adhesion assays, cell-CAM 105 had redistributed to all areas of the plasma membrane. Immunofluorescence analysis of primary hepatocyte cultures revealed that cell-CAM 105 and two other BC proteins were localized in discrete domains reminscent of BC while cell-CAM 105 was also present in regions of intercellular contact. These results indicate that the distribution of cell-CAM 105 under the experimental conditions used for cell adhesion assays differs from that in situ and raises the possibility that its adhesive function may be modulated by its cell surface distribution. The implications of these and other findings are discussed with regard to a model for BC formation.^ Analysis of molecular events involved in BC formation would be accelerated if an in vitro model system were available. Although BC formation in culture has previously been observed, repolarization of cell-CAM 105 and two other domain-specific membrane proteins was incomplete. Since DMSO had been used by Isom et al. to maintain liver-specific gene expression in vitro, the effect of this differentiation system on the polarity of these membrane proteins was examined. Based on findings presented here, DMSO apparently prolongs the expression and facilitates polarization of hepatocyte membrane proteins in vitro. ^