Autocrine Down-Regulation of Basic Fibroblast Growth Factor Receptors Causes Mitotoxin Resistance in a Human Melanoma Cell Line

The ability of melanoma to develop resistance to mitotoxins, growth-factor- directed anti-neoplastic agents that offer potential for the treatment of this highly refractory disease, may limit therapeutic efficacy. To address this problem, we developed a subcloned human melanoma cell line that is resistant to the mitotoxin composed of basic fibroblast growth factor conjugated to the ribosome-inactivating protein saporin. Resistance was caused by autocrine FGF ligands, which down-regulate bFGF receptors and reduce bFGF-saporin binding. Inhibiting the autocrine loop with suramin or with neutralizing antibodies to FGF up-regulated receptors and decreased resistance in vitro. Furthermore, suramin restored sensitivity in resistant tumor xenografts. These results suggest the potential of therapeutic modalities combining agents that neutralize growth factors with receptor-directed mitotoxins for targeting malignant melanoma either to prevent emergence of resistance or to circumvent resistance once it occurs

Progress Report on Iowa State University Burroughs Endowment Activities

Faculty in the Department of Animal Science initiated soliciting of funds in 1987 to establish a permanent endowment to recognize the distinguished career and major contributions of Dr. Wise Burroughs, a distinguished professor in animal science at Iowa State University. The endowment was established in the Iowa State University Foundation in 1991. The purpose of the fund is to support research and graduate education in the areas of fundamental factors regulating growth in food-producing animals, with emphasis on ruminants; to enhance growth of animals with the goal of improving the competitive position of ruminants as food-producing animals; and to develop innovative approaches to ruminant nutrition and/or growth enhancement as a means to improve desirability of meat produced by food animals. Dr. Burroughs’ research resulted in important and significant developments in technology for modern production systems for beef cattle. He was widely known for his ability to communicate complex ideas and research results for use by those involved in the animal industry. The current Burroughs Team has established three research projects: 1) Ghrelin--How does ghrelin affect blood and body composition in rats?; 2) Use of 25- hydroxyvitamin D3 to improve tenderness of beef; 3) Redesigning beef cattle to have a more healthful fatty acid composition

Osteosarcomagenesis: Biology, Development, Metastasis, and Mechanisms of Pain

Osteosarcoma is the most common primary cancer of the bone and third most common cancer in children and adolescents with approximately 900 new cases annually in the United States. A major facet of osteosarcoma is its high level of genomic instability, in particular chromosomal instability, which is the result of increased or decreased chromosome number in a cell. Furthermore, pain is the most common symptomatic feature of osteosarcoma that lacks effective therapy. Pain in osteosarcoma is relatively more complicated than many other painful conditions requiring a more thorough understanding of its etiology, pathobiology, and neurobiology to allow the development of better therapies for reducing pain in osteosarcoma patients. Studies are underway to define the diverse modalities of presentation, growth, development, metastases, and nociception in osteosarcoma. New data from human studies in combination with data from studies incorporating transgenic mouse models of osteosarcoma are providing valuable insights into the mechanisms underlying the development of both the tumor and the tumor-induced pain. These new data will undoubtedly lead to improved prognoses, as well as the development of novel therapeutics that will significantly decrease bone cancer pain

1,25-Dihydroxyvitamin D3 Enhances Bovine Mammary Epithelial Innate Immune Responses

Bovine mammary epithelial cells that were treated with bacterial lipopolysaccharide and 1,25-dihydroxyvitamin D3 showed an increase in the expression of the genes for inducible nitric oxide synthase (iNOS) and S100 calcium binding protein A12 (S100 A12). iNOS and S100 A12 are part of the innate immune response and expressed in the mammary gland during mastitis. Production of 1,25- dihydroxyvitamin D3 in the mammary gland during mastitis, then, may be an important component of the innate immune response

Effects of Complete Vitamin and Mineral Supplementation in Full Potential All-milk Diets on Growth and Health of Holstein Bull Calves

Pre-ruminant Holstein bull calves were fed two diets of pasteurized whole milk (PWM) in amounts that either limited intake or that maximized intake according to common commercial practice. Diets then were either supplemented or not supplemented with a full complement of vitamins and trace minerals (VTM) that met or exceeded NRC requirements. The objective of the study was to quantify the effects of the four feeding strategies on growth of calves, vitamin and mineral statuses in blood, and magnitude of acute phase inflammatory protein expression in response to lipopolysaccharide (LPS) exposure. Calves were assigned randomly to one of four treatment groups (LM-, low milk, not VTM supplemented; LM+, low milk, TMV supplemented; HM-, high milk, not VTM supplemented; HM+, high milk, TMV supplemented) for 15 days. The HM strategy increased average daily gain in calves, but VTM supplementation did not improve growth during the first two weeks of life. Calves fed more milk had greater magnesium and copper concentrations in blood plasma, but treatment groups did not differ in acute phase protein expression

Early Inflammation Disorder in Neonatal Calves

In the present study, 30 Holstein calves were acquired at birth and were randomly subjected to one of six treatments. One treatment group was colostrum deprived (CD) and five other treatment groups were fed colostrum replacer (CR). Of the five CR groups, one group was not further supplemented (CR), one received vitamin A (CR-A), one received vitamin D (CR-D), one received vitamin E (CR-E), and one received vitamins A, D, and E (CR-ADE). Additionally, all calves were inoculated with Mycobacterium avium, subsp. paratuberculosis on d 1 and d 3 of age. One d after birth, CD calves exhibited lower IgG1, haptoglobin, and serum amyloid A concentrations in serum compared with the other five CR groups. These findings point to an endogenous early inflammation disorder in calves that are not fed colostrum

Astrochemistry and Astrophotonics for an Antarctic Observatory

Due to its location and climate, Antarctica offers unique conditions for long-period observations across a broad wavelength regime, where important diagnostic lines for molecules and ions can be found, that are essential to understand the chemical properties of the interstellar medium. In addition to the natural benefits of the site, new technologies, resulting from astrophotonics, may allow miniaturised instruments, that are easier to winterise and advanced filters to further reduce the background in the infrared.Comment: 4 pages, to be published in EAS Publications Series, Vol. 40, Proc. of 3rd ARENA conferenc

Use of Glucagon to Prevent and Treat Fatty Liver in Transition Dairy Cows

Because of the relationship of fatty liver to increase health problems and decreased productive and reproductive performance, scientists can improve the profitability of dairy farmers by developing nutritional and management technologies for preventing and treating fatty liver. Our research group has demonstrated that glucagon shows much promise for use in preventing and treating fatty liver in transition cows. Moreover, we have data to indicate that ultrasound technology can be used to estimate the incidence of fatty liver within a dairy herd. The development of a slow-release form of glucagon would seem necessary before adoption of our proposed glucagon technology is adopted by the dairy industry

Regulation of Immune Responses to Mycobacteria bovis by a Paracrine Mechanism of Vitamin D Signaling in Cattle

We provide evidence that T-cell responses to Mycobacteria bovis are suppressed by the production of 1,25-dihydroxyvitamin D3 in monocytes and B-cells from cattle. Current vitamin D requirements for cattle are solely based on the classical endocrine mechanism of vitamin D signaling that regulates calcium homeostasis and should be re-evaluated to account for vitamin D signaling mechanisms in the immune system

Health and Reproductive Performance of Lactating Dairy Cows with Mild Fatty Liver Receiving Exogenous Glucagon

The data demonstrate that mild fatty liver is associated with decreased general health and reproductive performance as evidenced by more days to first estrus and service, more days open, decreased conception, increased number of days with elevated body temperature at days 9 - 22 postpartum, and increased incidence of mastitis at days 32 – 150 postpartum. The latter two were decreased in dairy cows with mild fatty liver injected with 15 mg/d of glucagon during weeks 2 and 3 postpartum. Therefore, treatment of mild fatty liver with exogenous glucagon or better prevention of fatty liver might improve health and reproductive performance of lactating dairy cows, thereby preventing loss of income of dairy farmers