In a cross-sectional study of the 1991 Peruvian cholera epidemic,
Vibrio cholerae 01 infection was associated with
Helicobacter pylori infection, particularly in young children. These data support ...the hypothesis that hypochlorhydria induced by
H pylori is important in the pathogenesis of diarrhoeal disease.
We report on the effect of retrace error during measurement of freeform optics using a commercial coherence scanning interferometer (CSI), and its in-built stitching capabilities. It is shown that ...measuring segments of freeform optics under non-null conditions, results in artifacts on the measured zone, similar to the Seidel aberrations. An experimental approach is used to quantify the induced aberrations based on the local slopes of the surface. Simulation of surfaces containing different order aberrations is shown to have a significant effect on the measurement data. A correction method is proposed that uses experimental measurements to determine the required correction based on local slope and position in the aperture. These corrections reduce the measurement difference from a comparison measurement using a Fizeau interferometer.
Noninvasive methods for measuring the pharmacokinetics of chemotherapeutic drugs such as 5-fluorouracil (FU) are needed for individualized optimization of treatment regimens. PET imaging of 18FFU ...(PET/18FFU) is potentially useful in this context, but PET/18FFU is severely hampered by low tumor uptake of radiolabel and rapid catabolism of FU in vivo. Pretreatment with eniluracil (5-ethynyluracil) prevents catabolism of FU. Hypothesizing that suppression of catabolism would enhance PET/18FFU, we examined the effects of eniluracil on the short-term pharmacokinetics of the radiotracer.
Anesthetized rats bearing a subcutaneous rat colorectal tumor were given eniluracil or placebo and injected intravenously 1 h later with 18FFU or 3HFU. In the 18F studies, dynamic PET image sequences were obtained 0-2 h after injection. Tumors were excised and frozen at 2 h and then analyzed for labeled metabolites by high-performance liquid chromatography. Biodistribution of radiolabel was determined by direct tissue assay.
Eniluracil improved tumor visualization in PET images. With eniluracil, tumor standardized uptake values (activity/g/injected activity/g body weight) increased from 0.72 +/- 0.06 (mean +/- SEM; n = 6) to 1.57 +/- 0.20 (n = 12; P < 0.01), and tumor uptake increased by factors of 2 or more relative to plasma (P < 0.05) and bone, liver, and kidney (P < 0.01). Without eniluracil (n = 5), 57% +/- 4% of recovered radiolabel in tumor at 2 h was on catabolites, with the rest divided among FU (2% +/- 1%), anabolites of FU (38% +/- 7%), and unidentified peaks (4% +/- 2%). With eniluracil (n = 8), catabolites, FU, and anabolites comprised 2% +/- 1%, 41% +/- 5%, and 57% +/- 4%, respectively, of the recovered radiolabel in tumors.
Eniluracil increased tumor accumulation of 18F relative to host tissues and fundamentally changed the biochemical significance of that accumulation. With catabolism suppressed, tumor radioactivity reflected the therapeutically relevant aspect of FU pharmacokinetics--namely, uptake and anabolic activation of the drug. With this approach, it may be feasible to measure the transport and anabolism of 18FFU in tumors by kinetic modeling and PET. Such information may be useful in predicting and increasing tumor response to FU.
FADD (also known as Mort-1) is a signal transducer downstream of cell death receptor CD95 (also called Fas). CD95, tumor necrosis factor receptor type 1 (TNFR-1), and death receptor 3 (DR3) did not ...induce apoptosis in FADD-deficient embryonic fibroblasts, whereas DR4, oncogenes E1A and c-myc, and chemotherapeutic agent adriamycin did. Mice with a deletion in the FADD gene did not survive beyond day 11.5 of embryogenesis; these mice showed signs of cardiac failure and abdominal hemorrhage. Chimeric embryos showing a high contribution of FADD null mutant cells to the heart reproduce the phenotype of FADD-deficient mutants. Thus, not only death receptors, but also receptors that couple to developmental programs, may use FADD for signaling.
The thymidine analog 2′-fluoro-5-methyl-1-β-
d-arabinofuranosyluracil (FMAU) is incorporated into DNA and is resistant to catabolism. We performed pharmacokinetic measurements with
14CFMAU and PET ...studies with
11CFMAU using rats bearing several different syngeneic tumors. Among normal tissues, FMAU uptake reflected relative cell turnover rates. Among tumors, the highest uptake occurred in a rapidly growing colon carcinoma, but was similarly low in both rapidly and slowly growing prostate tumors. FMAU was not catabolized and was rapidly incorporated into DNA by small intestine and colon tumors. Results indicate that FMAU may be useful for imaging tissue DNA synthesis, although tumor uptake was modest and not well correlated with growth rate among the models examined.
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