Water immersion increases urinary excretion of aquaporin-2 in healthy humans

Many previous studies have shown that aquaporin-2 (AQP2), the vasopressin-regulated water channel, is excreted in the urine and that the excretion increases in response to vasopressin. Moreover, recently a close correlation between AQP2 excretion in urine and kidney AQP2 expression has been demonstrated, showing that urinary excretion of AQP2 is a reliable indicator for AQP-2 function. As head-out water immersion causes an expansion in the central vascular volume equal to that induced by 2 liters of saline, without modifying plasma composition, we used immersion in water to evaluate if the response to acute expansion of the central vascular volume could involve vasporessin (AVP) and AQP2. In healthy subjects, concentrations of plasma atrial natriuretic factor (ANF) and AVP, and urinary AQP2 were measured during a 2-hour immersion period. In all subjects, immersion caused a prompt and marked increase in immunoreactive ANF (23.0 +/- 2.12 pg/ml at second hour vs. 2.17 +/- 0.42 pg/ml at baseline) and in urinary excretion of AQP2 (23.9 +/- 2. 69 pmol/mg creatinine at second hour vs. 4.42 +/- 0.14 pmol/mg creatinine at baseline), while a significant decrease was found in plasma AVP. Recovery was associated with a prompt return to pre-study levels. These findings demonstrate that heat-out water immersion stimulates urinary excretion of AQP2 in absence of an increase in plasma AVP.     

Long Term Trends and Racial/Ethnic Disparities in the Prevalence of Obesity

Obesity is an epidemic associated with higher rates of hypertension, diabetes, and cardiovascular diseases. However, significant racial disparities in the prevalence of obesity have been reported. To evaluate racial disparities and trends in the prevalence of obesity and obesity-related diseases. A population-based retrospective cohort study utilized data from the 1985 to 2011 California Behavioral Risk Factor Survey. Trends in obesity prevalence were stratified by age, sex, race/ethnicity, and socioeconomic factors. Multivariate logistic regression models evaluated independent predictors of obesity. The prevalence of obesity in significantly increased from 1985 to 2011 (8.6 vs. 22.8 %, p < 0.001). This increase was seen among men and women, and among all race/ethnic, age, and socioeconomic groups. Hypertension and diabetes also increased during this time period (hypertension 20.7–35.9 %; diabetes 4.2–11.2 %). Obesity prevalence was highest in blacks and Hispanics, and lowest in Asians (blacks 33.3 %; Hispanics 28.8 %; Asians 9.0 %; p < 0.001). Obesity prevalence was associated with lower education level, lower income, and unemployment status. After adjustments for age, sex, co morbidities, and surrogates of socioeconomic status, the increased risk of obesity in blacks and Hispanics persisted (blacks OR 1.51; Hispanics OR 1.18), whereas Asians were less likely to be obese (OR 0.37). While the overall prevalence of obesity increased from 1985 to 2011, significant racial/ethnic disparities in obesity have developed, with the highest prevalence seen in blacks and Hispanics, and the lowest seen in Asians.     

Both HCV and HBV are Major Causes of Liver Cancer in Southeast Asians

The incidence of hepatocellular carcinoma (HCC) is higher in Asian Americans than in other ethnicities. While hepatitis B virus (HBV) is common, hepatitis C virus (HCV) is more prevalent in some subgroups. Our goal was to determine the etiology of liver disease associated with HCC in subgroups of Asian Americans. This was an analysis of 510 Asian HCC patients at a US medical center. Patients were identified using ICD9 diagnosis. Multivariate logistic regression was used to study predictors of HCV as the cause of HCC. Patients were Southeast Asian, Chinese, and Korean, with similar gender, age, and foreign-born status. Southeast Asians had a similar proportion of HBV- and HCV-related HCC, while Chinese and Korean patients had a higher proportion of HBV-related HCC. HCC was usually associated with HBV in Chinese and Korean patients, but both HCV and HBV were important associations in Southeast Asians.     

Detecting EGFR alterations in clinical specimens—pitfalls and necessities

We investigated the epidermal growth factor receptor (EGFR) status in early stage lung cancer in Southern Sweden, a population for which there are no previous reports on the EGFR mutation frequency. Three hundred fifty small cell lung cancers, adenocarcinomas (AC), squamous cell carcinomas (SqCC), and large cell carcinomas were analyzed using a combination of techniques for the analysis of protein expression, gene copy numbers, and mutations. Immunohistochemical (IHC) staining with antibodies for the EGFR mutations L858R and del E746-A750 revealed intratumoral heterogeneity and several discrepant cases when compared to mutation-specific polymerase chain reaction (PCR)-based analysis. The frequencies of these two mutations, when considering IHC staining with mutation-specific antibodies in a cohort of 298 cases and subsequent confirmation by PCR, were 10 % in AC and <2 % in SqCC. Furthermore, screening by sequencing of EGFR in a cohort of 52 lung AC and squamous carcinomas demonstrated a more diverse mutation spectrum, not covered by the mutation-specific antibodies. High expression of total EGFR protein was correlated to high gene copy numbers but did not reflect the mutational status of the tumors. We believe that the mutation spectra in a Southern Swedish population is too diverse to be covered by the mutation-specific antibodies, and we also raise some other issues regarding the use of the mutation-specific antibodies, for example concerning heterogeneous expression of the mutated protein, optimal antibody dilution, and discrepancies between staining results and PCR.     

TLR2- and Dectin 1–Associated Innate Immune Response Modulates T-Cell Response to Pancreatic β-Cell Antigen and Prevents Type 1 Diabetes

The progression of autoimmune diseases is dictated by deviations in the fine balance between proinflammatory versus regulatory responses, and pathogen recognition receptors (PRRs) play a key role in maintaining this balance. Previously, we have reported that ligation of Toll-like receptor 2 (TLR2) and Dectin 1 on antigen-presenting cells by zymosan results in a regulatory immune response that prevents type 1 diabetes (T1D). Here, we show that TLR2 and Dectin 1 engagement by zymosan promotes regulatory T-cell (Treg) responses against the pancreatic β-cell–specific antigen (Ag). Unlike the TLR4 ligand, bacterial lipopolysaccharide, which induced proinflammatory cytokines and pathogenic T cells, zymosan induced a mixture of pro- and anti-inflammatory factors and Tregs, both in vitro and in vivo. Ag-specific T cells that are activated using zymosan-exposed dendritic cells (DCs) expressed Foxp3 and produced large amounts of IL-10, TGF-β1, and IL-17. NOD mice that received β-cell-Ag–loaded, zymosan-exposed DCs showed delayed hyperglycemia. Injection of NOD mice at the prediabetic age and early hyperglycemic stage with β-cell-Ag, along with zymosan, results in a superior protection of the NOD mice from diabetes as compared with mice that received zymosan alone. This therapeutic effect was associated with increased frequencies of IL-10–, IL-17–, IL-4–, and Foxp3-positive T cells, especially in the pancreatic lymph nodes. These results show that zymosan can be used as an immune regulatory adjuvant for modulating the T-cell response to pancreatic β-cell-Ag and reversing early-stage hyperglycemia in T1D.     

Challenges and strategies in recruiting, interviewing, and retaining recent Latino immigrants in substance abuse and HIV epidemiologic studies

The growth of immigrant populations in the United States over the past 20 years has increased the need to enhance understanding about the risk factors that influence their substance abuse and HIV risk behaviors. Today, Latinos account for the largest majority of immigrants gaining entry into the United States. As the largest and fastest growing minority subgroup in the United States, they bear a disproportionate burden of disease and death compared to non-Latinos. Latinos are confronted with escalating HIV and substance-abuse problems, particularly Latinos between the ages of 18-34. This paper is based on our longitudinal study on the drug using and HIV risk behaviors of 527 recent Latino immigrants between the ages of 18-34 who have lived in the United States less than 1 year. The data collection activities of this study have provided insights in identifying, recruiting, interviewing, and retaining Latinos in community-based studies. Strategies, such as utilizing a combination of translation techniques, ensured the development and implementation of culturally appropriate questionnaires. Respondent-driven sampling facilitated identifying participants. Establishing rapport and trust was critical for interviewing, and maintaining a tracking protocol was most important for retention. The lessons learned from this study can guide substance abuse and HIV researchers when recruiting, interviewing, and retaining recent Latino immigrants in future epidemiologic studies.