No abstract

Transgene expression in intact animals now can be visualized by noninvasive techniques. However, the instruments and protocols developed so far have been formidable and expensive. We describe here a system for rapidly visualizing transgene expression in major organs of intact live mice that is simple, rapid, and eminently affordable. Green fluorescent protein (GFP) is expressed in the cells of brain, liver, pancreas, prostate, and bone, and its fluorescence is encoded in whole-body optical images. For low-magnification images, animals are illuminated atop a fluorescence light box and directly viewed with a thermoelectrically cooled color chargecoupled device camera. Higher-magnification images are made with the camera focused through an epi-fluorescence dissecting microscope. Both nude and normal mice were labeled by directly injecting 8 ؋ 10 10 plaque-forming units͞ml of adenoviral GFP in 20 -100 l PBS and 10% glycerol into either the brain, liver, pancreas, prostate, or bone marrow. Within 5-8 h after adenoviral GFP injection, the fluorescence of the expressed GFP in brain and liver became visible, and whole-body images were recorded at video rates. The GFP fluorescence continued to increase for at least 12 h and remained detectable in liver for up to 4 months. The system's rapidity of image acquisition makes it capable of real-time recording. It requires neither exogenous contrast agents, radioactive substrates, nor long processing times. The method requires only that the expressed gene or promoter be fused or operatively linked to GFP. A comparatively modest investment allows the study of the therapeutic and diagnostic potential of suitably tagged genes in relatively opaque organisms.green fluorescent protein fluorescence optical imaging ͉ in vivo gene expression ͉ real time

Among 1001 patients with carcinoma of the pancreas, 23 of 912 patients with exocrine carcinomas, 10 of 46 with ampullary carcinomas, and 21 of 43 with malignant islet cell tumors survived 3 years. Of the survivors with exocrine cancers, there were nine of 97 patients who had curative operation, two had had palliative resections only, and one was an incidental microfocal carcinoma; in the remaining 11 patients a histologic origin in the pancreas was not established. Preoperatively suspected and histologically proven 3-year survivors included six patients with ductal adenocarcinomas, three patients with mucinous cystadenocarcinomas, one patient with acinic cell carcinoma, and one patient with microadenocarcinoma. Only two patients can be considered cured. Tumor size and lymph node status did not correlate with survival. Cystadenocarcinomas comprised 1% of cases but one third of 3-year survivors. Long-term survival in histologically confirmed pancreatic carcinoma is a rare event that cannot be predicted in the individual case.

Troglitazone is a new orally active hypoglycemic agent that has been shown to reduce insulin resistance and hyperinsulinemia in both diabetic animal models and non-insulin-dependent diabetes mellitus (NIDDM) subjects. To determine whether this drug could prevent the development of fructose-induced insulin resistance and related abnormalities, we studied the effects of troglitazone on the insulin resistance induced by fructose feeding in rats. Normal male Sprague-Dawley rats were fed a high-fructose diet for 3 weeks with and without troglitazone as a food admixture (0.2%) or were fed normal chow to serve as a control group. In vivo insulin resistnace was measured by the euglycemic hyperinsulinemic clamp technique at two different insulin infusion rates, 29 (submaximal stimulation) and 290 (maximal stimulation) pmol.kg-1.min-1. Fructose feeding markedly reduced submaximal glucose disposal rate (GDR) (113.8 +/- 8.3 vs. 176.0 +/- 5.6 mumol.kg-1.min-1, P < 0.05) and maximal GDR (255.9 +/- 5.6 vs. 313.6 +/- 10.5 mumol.kg-1.min-1, P < 0.05), reduced the suppressibility of submaximal hepatic glucose production (HGP; 45.5 +/- 5.0 vs. 11.7 +/- 5.0 mumol.kg-1.min-1, P < 0.05), and resulted in hypertriglyceridemia and hypertension. Troglitazone treatment completely restored the GDR (submaximal 158.2 +/- 5.6, maximal 305.3 +/- 6.1 mumol.kg-1.min-1) and submaximal HGP (9.4 +/- 2.8 mumol.kg-1.min-1) to control levels and also normalized the elevated plasma triglyceride concentration and systolic blood pressure levels in fructose-fed rats.(ABSTRACT TRUNCATED AT 250 WORDS)