Faculty Bibliography

Scientists have recently found that the strain of the avian influenza virus, known as A(H5N1), seems firmly rooted among domesticated ducks and wildlife and so cannot be wiped out by culling, quarantines and other standard measures alone, [Joseph Domenech] said. He spoke at a meeting attended by health officials from 10 Asian countries that the FAO convened in part to deal with a resurgence of avian influenza in China, Thailand and Vietnam and the virus' continuing spread in Indonesia. At the same time, many influenza experts and public health officials fear a scenario in which an individual becomes infected with both the A(H5N1) avian virus and a human influenza virus. Under such circumstances, the viruses could swap genes to create a new virus to cause a global epidemic that would be difficult to control. In the A(H5N1) epidemic in Southeast Asia, health workers are dealing with a situation that differs significantly from outbreaks of other strains of avian influenza. Those outbreaks, in developed countries in temperate regions, have been stopped by using vaccines as a short-term emergency measure in tandem with culling and other standard measures, said Mike Nunn, who manages Australia's Animal Health Science department, and Sarah Kahn, an Australian veterinary consultant to the Food and Agricultural Organization

PURPOSE/OBJECTIVE:We recently demonstrated that a polymorphism in codons 22 and 23 of the glucocorticoid receptor gene is associated with relative glucocorticoid resistance, greater insulin sensitivity, and lower total and low-density lipoprotein cholesterol levels. In the present study, we investigated whether the ER22/23EK polymorphism is associated with survival, cholesterol levels, and two predictors of mortality: serum C-reactive protein and interleukin 6 levels. METHODS:We studied 402 men (mean [+/- SD] age, 77.8 +/- 3.6 years). C-reactive protein was measured by a highly sensitive method using a latex-enhanced immunoephelometric assay. Interleukin 6 was determined by a commercially available immulite assay. RESULTS:After a follow-up of 4 years, 73 (19%) of 381 noncarriers died, while none of the 21 ER22/23EK carriers had died (P = 0.03). C-reactive protein levels were about 50% lower in ER22/23EK carriers (P = 0.01). There were no differences in interleukin 6 levels. CONCLUSION/CONCLUSIONS:Carriers of the ER22/23EK polymorphism have better survival than noncarriers, as well as lower C-reactive protein levels.

The proopiomelanocortin-derived peptide, alpha-MSH, inhibits feeding via melanocortin receptors in the hypothalamus and genetic defects inactivating the melanocortin system have been shown to lead to obesity in experimental animals and humans. To determine whether long-term melanocortinergic activation has significant effects on body weight and composition and insulin sensitivity, transgenic mice overexpressing N-terminal proopiomelanocortin, including alpha- and gamma(3)-MSH, under the control of the cytomegalovirus-promoter were generated. The transgene was expressed in multiple tissues including the hypothalamus, in which both alpha-MSH and gamma(3)-MSH levels were increased approximately 2-fold, compared with wild-type controls. Transgene homozygous mice were also crossed with obese leptin receptor-deficient db(3J) and obese yellow A(y) mice. MSH overexpression led to uniform, dose- dependent darkening of coat color. MSH overexpression reduced weight gain and adiposity and improved glucose tolerance in lean male mice. In female transgenic mice, there was no significant effect on body weight, but there was a significant decrease in insulin levels. Obesity was attenuated in obese db(3J)/db(3J) male and female mice, but there was no improvement in glucose metabolism. In contrast, the MSH transgene improved glucose tolerance in male A(y) mice. These results support the hypothesis that long-term melanocortinergic activation could serve as a potential strategy for anti-obesity and/or antidiabetic therapy.

BACKGROUND: Pinacidil solutions have been shown to have significant cardioprotective effects. Pinacidil activates both sarcolemmal and mitochondrial potassium-adenosine triphosphate (K(ATP)) channels. This study was undertaken to compare pinacidil solution with University of Wisconsin (UW) solution and to determine if the protective effect of pinacidil involved mitochondrial or sarcolemmal K(ATP) channels. METHODS: Thirty-two rabbit hearts received one of four preservation solutions in a Langendorff apparatus: (1) UW; (2) a solution containing 0.5 mmol/L pinacidil; (3) pinacidil with Hoechst-Marion-Roussel 1098 (HMR-1098), a sarcolemmal channel blocker; and (4) pinacidil with 5-hydroxydecanote, a mitochondrial channel blocker. Left ventricular pressure-volume curves were generated by an intraventricular balloon. All hearts were placed in cold storage for 8 hours, followed by 60 minutes of reperfusion. RESULTS: Postischemic developed pressure was better preserved by pinacidil than by UW. This cardioprotective effect was eliminated by 5-hydroxydecanote and diminished by HMR-1098. Diastolic compliance was better preserved by pinacidil when compared with UW. This protection was abolished by the addition of 5-hydroxydecanote and moderately decreased by HMR-1098. CONCLUSIONS: Our results support the superiority of pinacidil over UW after 8 hours of storage. The cardioprotective role of pinacidil is mediated primarily by the mitochondrial K(ATP) channel

Parathyroid hormone (PTH) regulation of matrix metalloproteinase-13 (MMP-13) expression in osteoblasts contributes to normal bone turnover. The PTH response region of the rat MMP-13 gene spans nucleotides (nt) -148 to -38 and supports binding of numerous transcription factors, including Runx2, necessary for osteoblast differentiation, c-Fos/c-Jun, and Ets-1. These trans-acting proteins mediate hormone induction via incompletely defined combinatorial interactions. Within this region, adjacent to the distal Runx2 site, is a homopolymeric(dA:dT) element (-119/-110 nt) that conforms to the consensus site for the novel transcription factor nuclear matrix protein-4/cas interacting zinc finger protein (Nmp4/CIZ). This protein regulates bone cell expression of type I collagen and suppresses BMP2-enhanced osteoblast differentiation. The aim of this study was to determine whether Nmp4/CIZ contributes to MMP-13 basal transcription and PTH responsiveness in osteoblasts. Electrophoretic mobility shift analysis confirms Nmp4/CIZ binding within the MMP-13 PTH response region. Mutation of the Nmp4/CIZ element decreases basal activity of an MMP-13 promoter-reporter construct containing the first 1329 nt of the 5'-regulatory region, and overexpression of Nmp4/CIZ protein enhances the activity of the wild-type promoter. The same mutation of the homopolymeric(dA:dT) element enhances the MMP-13 response to PTH and PGE(2). Overexpression of Nmp4/CIZ diminishes hormone induction. Mutation of both the homopolymeric(dA:dT) element and the adjacent Runx2 site further augments the PTH response. On the basis of these data and previous studies, we propose that Nmp4/CIZ is a component of a multiprotein assemblage or enhanceosome within the MMP-13 PTH response region and that, within this context, Nmp4/CIZ promotes both basal expression and hormonal synergy

The tobacco industry recently introduced a new set of 'safe' cigarettes and nicotine delivery devices that purportedly entail reduced tobacco-related disease risk due to their lower level of some carcinogens and toxins. Little is know about the biological impact of these potential reduced exposure products (PREPs) and nothing is known about their advertising and availability. Hence, two pilot studies were conducted to examine the latter issues for the first time. In Study 1, we examined tobacco ads in 10 popular magazines 1998--2002 and found that only 1% of ads were for PREPs. In Study 2, we attempted to purchase PREPs in a random sample of 113 small stores and found that only 4.4% sold any PREP. These preliminary findings tentatively suggest that the industry might not yet be heavily invested in products that have the potential to increase tobacco use by decreasing its perceived harm. Studies with larger samples are recommended

The strain of the avian influenza virus, known as A(H5N1), is gaining a stronger foothold in Asia, health officials said on Friday at the end of a three-day meeting on the disease. The United Nations has called the scope of the spread of avian influenza in Asia and its effect on the livelihood and nutrition of people there 'unprecedented.' UN officials have also called continued presence of A(H5N1) a threat to human health because it has become increasingly virulent and because it could combine with a human influenza virus to create a new one that could cause a worldwide influenza epidemic. 'The epidemiology of avian influenza is very complex' in part because of the differences in geography, culture and farming systems, [Joseph Domenech] said. 'This makes it very difficult to obtain a precise understanding of the crisis and definition of required control plans.' Theories include biological changes in the virus; premature restocking of poultry farms, and improved surveillance and awareness with earlier detection and more prompt reporting of cases

The strain of the avian influenza virus, known as A(H5N1), is gaining a stronger foothold in Asia, health officials said Friday at the end of a three-day meeting. The United Nations has called the scope of its spread in Asia and its effect on the livelihood and nutrition of people there ''unprecedented.'' Dr. He said experts did not know whether the new outbreaks were part of the continuing incidence of avian influenza or were brought by wild and migratory birds. Scientists also do not know precisely how the virus is transmitted or how it produces disease in animals and humans. In general terms, it is spread by exposure to infected poultry, their feces and contaminated soil. In addition to Thailand, the countries taking part in the new network are Cambodia, Laos, Indonesia, Malaysia, Myanmar, Papua New Guinea, the Philippines, East Timor and Vietnam. The Food and Agricultural Organization said it would create two more networks for other Asian regions