Abstract
There is increasing concern that the extensive use of antibiotics in agriculture is contributing to the emergence of antibiotic-resistant human bacterial pathogens. One way agricultural antibiotic use may result in antigen resistant bacterial infections is by selecting for antibiotic-resistant commensal organisms that humans obtain from food, water, or other humans. These commensal organisms may subsequently cause opportunistic human infections. Investigators in Baltimore developed a mathematical model of the effect of agricultural antibiotic use on antibiotic resistance in commensal bacteria that opportunistically infect man. Their model indicated that agricultural antibiotic use has little impact on the prevalence of antibiotic resistance in human commensals, although it accelerates the appearance of antibiotic-resistant strains of these bacteria. Based on this model, the investigators suggested that restricting agricultural use of specific antibiotics would be useful when bacteria resistant to the organism were rare, but would have little effect after antibiotic resistance had been established in the human population.
Smith DL, Harris AD, Johnson JA, Silbergeld EK, Morris JG: Animal antibiotic use has an early but important impact on the emergence of antibiotic resistance in human commensal bacteria. Proc Natl Acad Sci (USA) 99: 6434–6439, 2002
European researchers have described a model of cancer metastasis to bone using a human mammary tumor cell line introduced into athymic mice by intracardiac injection. Prior to injection, mammary epithelial cells were stably transfected with the luciferase gene. Cells were detected in vivo by intraperitoneal injection of luciferin followed by visualization using bioluminescent reporter imaging. Tumor cells were first detected in bones 24 days after injection of 105 cells, and bioluminescence increased over the subsequent weeks. The imaging technique detected as few as 104 cells per bone site, and there were approximately 6 bone sites per mouse. This imaging technique was markedly more sensitive than radiography for detecting sites of bone metastasis. Furthermore, because imaging was carried out in vivo, the technique allowed tumor development to be followed over time. This model will be useful for studying the molecular mechanisms of metastasis and for evaluating therapeutic strategies.
Wetterwald A, van der Pluijm G, Que I, Sijmons B, Buijs J, Karperien M, Lowik CW, Gautschi E, Thalmann GN, Cecchini MG. Optical imaging of cancer metastasis to bone marrow: a mouse model of minimal residual disease. Am J Pathol 160: 1143–1153, 2002
There are a variety of causes for the troublesome phenomenon of tissue autofluorescence. A recently described technique markedly reduced autofluorescence from all causes by photobleaching histologic sections. Sections 5 μm thick were mounted on glass slides and irradiated for 12–48 hours with lamps that emitted visible or long wavelength ultraviolet light. Most autofluorescence in human brain tumor and mouse liver tissue was eliminated by 24 hours of irradiation. In general, photobleaching did not affect the ability of antigens to bind fluorescent antibodies; however, cooling was recommended for heat-labile antigens.
Neumann M, Gabel D. Simple method for reduction of autofluorescence in fluorescence microscopy. J Histochem Cytochem 50: 437–439, 2002
A variety of studies have suggested that adult bone marrow contains stem cells that can differentiate into a variety of cell lineages when grown in the presence of pleuripotent embryonic stem cells or blastocyst cells. However, studies by American scientists indicated that the apparent maturation of bone marrow cells could also occur when the marrow cells fused with other cells and adopted their phenotype. These researchers fused green fluorescence protein-expressing bone marrow cells from female mice with male murine embryonic stem cells. When these cells were forced to differentiate in vitro, the cells that emerged expressed green fluorescent protein and appeared to have arisen by differentiation of adult bone marrow cells. However, further studies indicated that the cells were polyploid and contained Y chromosomes. Thus, the bone marrow cells had fused with the stem cells and acquired their differentiation potential.
Terada N, Hamazaki T, Oka M, Hoki M, Mastalerz DM, Nakano Y, Meyer EM, Morel L, Petersen BE, Scott EW. Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion. Nature 416: 542–545, 2002
Prion diseases such as scrapie are neurodegenerative diseases that are believed to be transmitted by an infectious agent composed only of protein. The incubation period for experimentally transmitted prion disease is determined by the host, the route of inoculation, and the titer of the inoculum. When investigators compared the disease caused by inoculation of high and low doses of mouse-adapted scrapie isolates, it was discovered that there was a marked difference in the severity of clinical signs produced. Mice that received high-dose inocula developed rapidly progressive terminal disease, while mice that received low doses developed reversible clinical signs and did not succumb to terminal disease. The grains of mice with both high and low-dose prion inocula had high levels of infectivity and contained abnormal PrP protein. Thus, it seemed that the dose of initial infective inoculum markedly altered the course of prion disease even when brains eventually came to contain comparable amounts of infectious material.
Thackray AM, Klein MA, Aguzzi A, Bujdoso R. Chronic subclinical prion disease induced by low-dose inoculum. J Virol 76: 2510–2517, 2002