Increased tissue resistance in the nude mouse against Candida albicans without altering strain-dependent differences in susceptibility

Strain differences in tissue responses to infection with Candida albicans were examined in nude mice having susceptible (CBA/CaH) and resistant (BALB/c) parentage. Homozygous (nu/nu) mice of both strains were more resistant to systemic infection with C. albicans than heterozygous (nu/+) littermates as indicated by a reduction in both the severity of tissue damage and colony counts in the brain and kidney. However, the tissue lesions in nu/nu CBA/CaH mice were markedly more severe than those in nu/nu mice with the BALB/c background. This pattern was reflected in the greater fungal burden in the CBA/CaH strain. Analysis of cDNA from infected tissues using a competitive polymerase chain reaction excluded interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), and interleukin 6 (IL-6) as mediators of the enhanced resistance of the nude mice. The results confirm that the different patterns of lesion severity in BALB/c and CBA/CaH mice do not involve T lymphocyte-mediated pathology, and are consistent with the hypothesis that strain-dependent tissue damage is not dependent on the effector function of macrophages or their precursors.

Long circulating half-life and high tumor selectivity of the photosensitizer meta-tetrahydroxyphenylchlorin conjugated to polyethylene glycol in nude mice grafted with a human colon carcinoma.

In a mode of nude mice bearing a human colon carcinoma xenograft, the biodistribution and tumor localization of metatetrahydroxyphenylchlorin (m-THPC) coupled to polyethylene glycol (PEG) were compared with those of the free form of this photosensitizer used in photodynamic therapy (PDT). At different times after i.v. injection of both forms of 125I-labeled photosensitizer, m-THPC-PEG gave on average a 2-fold higher tumor uptake than free m-THPC. In addition, at early times after injection, m-THPC-PEG showed a 2-fold longer blood circulating half-life and a 4-fold lower liver uptake than free m-THPC. The tumor to normal tissue ratios of radioactivity concentrations were always higher for m-THPC-PEG than for free m-THPC at any time point studied from 2 to 96 hr post-injection. Significant coefficients of correlation between direct fluorescence measurements and radioactivity counting were obtained within each organ tested. Fluorescence microscopy studies showed that m-THPC-PEG was preferentially localized near the tumor vessels, whereas m-THPC was more diffusely distributed inside the tumor tissue. To verify whether m-THPC-PEG conjugate remained phototoxic in vivo, PDT experiments were performed 72 hr after injection and showed that m-THPC-PEG was as potent as free m-THPC in the induction of tumor regression provided that the irradiation does for m-THPC-PEG conjugate was adapted to a well-tolerated 2-fold higher level. The overall results demonstrate first the possibility of improving the in vivo tumor localization of a hydrophobic dye used for PDT by coupling it to PEG and second that a photosensitizer conjugated to a macromolecule can remain phototoxic in vivo.

Selective tumor localization of radiolabeled anti-human melanoma monoclonal antibody fragment demonstrated in the nude mouse model.

Monoclonal antibodies (Mab) directed against distinct epitopes of the human 240 kD melanoma-associated antigen have been evaluated for their capacity to localize in human melanoma grafted into nude mice. A favorable tumor to normal tissue ratio of 13 was obtained with intact 131I-labeled MAb Me1-14. This ratio was further increased to 43 and 23 by the use of F(ab')2 and Fab fragments, respectively. The specificity of tumor localization was demonstrated by the simultaneous injection of F(ab')2 fragments from MAb Me1-14 and anti-CEA MAb 35, each labeled with a different iodine isotope, into nude mice grafted with a melanoma and colon carcinoma. The fragments from both MAb localized with perfect selectivity in their relevant tumor as shown by differential whole body scanning and by direct measurement of the two isotopes in tumors and normal tissues. These in vivo experimental results suggest that the F(ab')2 fragment from MAb Me1-14 is suitable for melanoma detection by immunoscintigraphy in patients.

An Ethical History of Photography in Combat and of Combat Photography in the United States during World War II

With the United States‘ entry into the Second World War, the word ?censorship? was seen largely as antithetical to, rather than a necessary counterpart to, victory among Americans. People did not want to be censored in their writing, photographs or speech,but it proved to be necessary even before the war began, in order to protect government secrets and the people on the home-front from scenes that were too disturbing. Even before the war had officially begun, there were problems with censorship among journalists and newspapers. The initial response of outrage in reference to censorship in the United States was common among journalists, newspapers, magazines, and radio news; nevertheless, there was a necessity for censorship among Americans, on the home frontand the front lines, and it would be tolerated throughout the war to ensure that enemies of America did not gain access to information that would assist in a defeat of the United States in the Second World War. The research I have conducted has dealt with the censorship of combat photography during World War II, in conjunction with the ethics that were in play at the time that affected the censors. Through exploring the work of three combat photographers — Tony Vaccaro, James R. Stephens and Charles E. Sumners — I wasable to effectively construct an explanatory ethical history of these three men. Research on the censorship and effects it had on the United States brought me to three distinctareas of censorship and ethics that would be explored: (1) the restrictions and limitations enforced by the Office of Censorship, (2) a general overview of war and photography as it influenced the soldiers and their families on the home-front, (3) and the combat photographers and personal and military censorship that influenced their work. Although their work was censored both by the military and the government, these men saw the war in a different light that remained with them long after the battles and war had ceased.Using the narratives of Tony Vaccaro, Charles E. Sumners and James R. Stephens as means for more in depth research, this thesis strives to create lenses through which to view the history and ethics of censorship that shaped combat photography during the Second World War and the images to which we refer as representative of that war today.