Occupational and environmental health in the 21st century: the new frontier in genetics and disease prevention.

Society is currently on the threshold of a new revolution in understanding the interaction of genes and the environment. This research has profound implications for understanding occupational disease and will present ethical challenges to occupational health practice. The public must be educated about the potential promise, as well as the threats, posed by emerging genetic technologies.     

Allopregnanolone produces hyperphagia by reducing neophobia without altering food palatability.

The neurosteroid allopregnanolone may increase feeding by altering food palatability; however, it may also increase feeding by reducing anxiety (neophobia). Moreover, it is unclear whether this induced hyperphagia is selective to safe, palatable foods only. Male rats were injected with allopregnanolone 20 min prior to behavioral testing. The taste reactivity test was used to examine possible shifts in the palatability of a 0.3 M sucrose solution. A lickometer was used to monitor intake and licking of either a sucrose or sucrose-quinine solution. Sucrose palatability was not enhanced; however, allopregnanolone significantly increased sucrose intake and licking on Test Day 1 when the solution was novel, but not on Test Day 2 when the solution was familiar. Sucrose-quinine intake was not enhanced. Allopregnanolone-induced hyperphagia is not a result of altered sucrose palatability, but rather reflects a reduction in the neophobia elicited by a novel solution; an effect that further seems to be selective to safe, palatable foods.     

GLUT1 and GLUT8 in endometrium and endometrial adenocarcinoma.

Glucose is provided to cells by a family of glucose transport facilitators known as GLUTs. These transporters are expressed in a tissue specific manner and are overexpressed in many primary tumors of these tissues. Regulation of glucose transport facilitator expression has been demonstrated in endometrial tissue and endometrial adenocarcinoma. The following experiments were conducted to quantify and localize the expression of GLUT1 and GLUT8 in benign endometrium and compare this expression to endometrial cancer. Endometrial tissue samples were obtained from random hysterectomy specimens of patients with benign indications for surgery and endometrial cancer. Immunoblot and immunolocatization studies were performed using GLUT1 and GLUT8 specific antisera. Endometrial samples from 65 women who had undergone hysterectomy were examined (n=38 benign, n=27 malignant). A 44 and a 35.4 kDa immunoreacive species was demonstrated in endometrium and endometrial cancer for GLUT1 and GLUT8, respectively. Upregulation of GLUT1 expression was demonstrated with increasing grade of tumors (P<0.002). GLUT8 expression was increased in all tumor subtypes compared to atrophic endometrium (P<0.001). Apical localization by GLUT1 and GLUT8 was demonstrated in endometrial glands. GLUT1 and GLUT8 demonstrated diffuse intracellular localization in the cancer subtypes. GLUT1 and GLUT8 are expressed in both human endometrium and endometrial cancer. There appears to be a step-wise progression in GLUT1 and GLUT8 expression as tumor histopathology worsens. GLUT1 and GLUT8 may be important markers in tumor differentiation, as well as providing energy to rapidly dividing tumor cells.     

Genotype prevalence and risk factors for severe clinical adenovirus infection, United States 2004-2006.

BACKGROUND: Recently, epidemiological and clinical data have revealed important changes with regard to clinical adenovirus infection, including alterations in antigenic presentation, geographical distribution, and virulence of the virus. METHODS: In an effort to better understand the epidemiology of clinical adenovirus infection in the United States, we adopted a new molecular adenovirus typing technique to study clinical adenovirus isolates collected from 22 medical facilities over a 25-month period during 2004-2006. A hexon gene sequence typing method was used to characterize 2237 clinical adenovirus-positive specimens, comparing their sequences with those of the 51 currently recognized prototype human adenovirus strains. In a blinded comparison, this method performed well and was much faster than the classic serologic typing method. RESULTS: Among civilians, the most prevalent adenovirus types were types 3 (prevalence, 34.6%), 2 (24.3%), 1 (17.7%), and 5 (5.3%). Among military trainees, the most prevalent types were types 4 (prevalence, 92.8%), 3 (2.6%), and 21 (2.4%). CONCLUSIONS: For both populations, we observed a statistically significant increasing trend of adenovirus type 21 detection over time. Among adenovirus isolates recovered from specimens from civilians, 50% were associated with hospitalization, 19.6% with a chronic disease condition, 11% with a bone marrow or solid organ transplantation, 7.4% with intensive care unit stay, and 4.2% with a cancer diagnosis. Multivariable risk factor modeling for adenovirus disease severity found that age <7 years (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.4-7.4), chronic disease (OR, 3.6; 95% CI, 2.6-5.1), recent transplantation (OR, 2.7; 95% CI, 1.3-5.2), and adenovirus type 5 (OR, 2.7; 95% CI, 1.5-4.7) or type 21 infection (OR, 7.6; 95% CI, 2.6-22.3) increased the risk of severe disease.     

Association of a 70-kDa tyrosine phosphoprotein with the CD16:ζ:γ complex expressed in human natural killer cells

The CD16: ζ: γ receptor complex allows natural killer (NK) cells to recognize and eliminate antibody-coated target cells. Whereas the ectodomain of CD16 is the receptor for Fcγ domains of immunoglobulins, disulfide-linked homo- and heterodimers composed of ζ and γ are required for the cell surface expression, and signal transduction properties of the complex. Engagement of CD16 activates the tyrosine kinase pathway, which induces the tyrosine phosphorylation of several substrates, including the ζ subunit and the phospholipase C γ-1 and γ-2 isoforms. Here we show that CD 16 stimulation of either peripheral blood NK cells, leukemic NK cells, or Jurkat transformants expressing a CD16:ζ:γ receptor complex, results in the tyrosine phosphorylation of a 70 kDa ζ-associated protein (pp70). Similarly, a 70-kDa ζ-associated phosphoprotein in T cells has been shown to be a tyrosine kinase (ZAP-70). Peptide mapping analysis indicates that the 70-kDa ζ-associated phosphoproteins from T cells and NK cells are structurally indistinguishable. We conclude that the CD16:ζ:γ complex may use a ZAP-70-related non-receptor tyrosine kinase, in the CD16 signaling cascade leading to NK cell activation.     

Nutritional issues in pediatric inflammatory bowel disease.

Malnutrition, characterized by weight loss, growth failure and micronutrient depletion, are prominent features of inflammatory bowel disease (IBD) in the pediatric age group. Accurate evaluation of the patient's nutritional status and appropriate nutritional support, whether enteral or parenteral, constitute integral parts of the management of the growing child with IBD. Over the past two decades, a number of studies have supported the potential use of nutritional therapy to induce remission and to control disease activity in symptomatic Crohn's disease. More recently, preliminary studies on the use of dietary supplements of marine-oil-derived omega-3 fatty acids have also indicated a beneficial effect in IBD patients. In parallel with these clinical trials, scientific research has recently focused on the concept that specific dietary alterations can modulate the immune response. Components of the diet that may have particular relevance to mucosal immunity and the pathogenesis of IBD include polyunsaturated fatty acids, nucleotides, and amino acids such as glutamine and arginine. Future research in the interactions between specific nutrients and the immune system will likely increase our understanding of the causes of IBD, as well as enhance the development of novel nutritional therapies for IBD patients.