Noninvasive assessment of hepatobiliary and renal elimination of cysteinyl leukotrienes by positron emission tomography

N-Acetyl-leukotriene E4 has been identified as an endogenous, biologically less active cysteinyl leukotriene metabolite in rodents and humans. To evaluate the ratio of hepatobiliary to renal elimination of leukotrienes noninvasively by positron emission tomography (PET), we synthesized N-[11C]acetyl-leukotriene E4 by chemical N-acetylation of leukotriene E4. After the intravenous injection of N-[11C]acetyl-leukotriene E4 in normal rats and monkey, uptake by the liver and subsequent excretion into bile were largely responsible for its rapid elimination from blood. In the Cynomolgus monkey, renal excretion of the leukotriene into urine was of additional quantitative importance. Kinetic modeling indicated a mean transit time through the liver of 17 minutes and 34 minutes in rat and monkey, respectively; the corresponding hepatic excretion half-times amounted to 8.5 minutes and 16 minutes. In a mutant rat strain deficient in the hepatobiliary excretion of cysteinyl leukotrienes across the canalicular membrane, the apparent mean liver transit time was 54 minutes, and the hepatic excretion half-time was 29 minutes, indicating prolonged organ storage and metabolism. After transport from the liver back into the circulating blood of omega-oxidized and beta-oxidized metabolites of N-[11C]acetyl-leukotriene E4, renal excretion compensated for the impairment of hepatobiliary elimination in the transport mutant. Metabolite analyses in urine after intravenous injection of N-[3H]acetyl-leukotriene E4 indicated the extensive inactivation of N-acetyl-leukotriene E4 by beta-oxidation from the omega-end in the mutants. A similar shift from hepatobiliary to renal cysteinyl leukotriene elimination was monitored in rats with cholestasis due to bile duct obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cigarette smoking, serum lipids, folate, and vitamin B12 in lung cancer

The purpose of our study was to evaluate the effects of cigarette smoking and serum lipids, folate, and vitamin B12 on the development of lung cancer in the Turkish population. The study group consisted of patients with histologically proven lung cancer and the control group comprised healthy smokers being followed in our smoking cessation outpatient department. Smoking history was obtained from all subjects and serum total cholesterol, HDL cholesterol, triglycerides, vitamin B12, and folate levels were measured. Pack/years of cigarettes smoked were significantly higher in the subjects with lung cancer than in the control group (p < 0.01). Serum total cholesterol, HDL cholesterol, triglyceride, serum folate, and vitamin B12 levels were within normal limits in both groups (p < 0.05), but serum vitamin B12 levels were statistically significantly higher (p < 0.01) in the cancer group than in the controls. In our study, we did not observe low levels of serum cholesterol, vitamin B12, or folate in the lung cancer patients.     

Passive navigation as a pattern recognition problem

The most basic visual capabilities found in living organisms are based on motion. Machine vision, of course, does not have to copy animal vision, but the existence of reliably functioning vision modules in nature gives us some reason to believe that it is possible for an artificial system to work in the same or a similar way. In this article it is argued that many navigational capabilities can be formulated as pattern recognition problems. An appropriate retinotopic representation of the image would make it possible to extract the information necessary to solve motion-related tasks through the recognition of a set of locations on the retina. This argument is illustrated by introducing a representation of image motion by which an observer's egomotion could be derived from information globally encoded in the image-motion field. In the past, the problem of determining a system's own motion from dynamic imagery has been considered as one of the classical visual reconstruction problems, wherein local constraints have been employed to compute from exact 2-D image measurements (correspondence, optical flow) the relative 3-D motion and structure of the scene in view. The approach introduced here is based on new global constraints defined on local normal-flow measurements—the spatio-temporal derivatives of the image-intensity function. Classifications are based on orientations of normal-flow vectors, which allows selection of vectors that form global patterns in the image plane. The position of these patterns is related to the 3-D motion of the observer, and their localization provides the axis of rotation and the direction of translation. The constraints introduced are utilized in algorithmic procedures formulated as search techniques. These procedures are very stable, since they are not affected by small perturbations in the image measurements. As a matter of fact, the solution to the two directions of translation and rotation is not affected, as long as the measurement of the sign of the normal flow is correct.Part of this work was accomplished while the author was visiting the Royal Institute of Technology, Stockholm, Sweden. The research was supported in part by ARPA, ONR, and Swedish National Science Foundation.     

Qualitativ-quantitative Simulation, ein Instrument zur Analyse nichtlinearer Regelkreise

Qualitative-quantitative simulation is one of the most productive and promising research areas in Artificial Intelligence to emerge in recent years. This method provides an elegant way for an exhaustive analysis of uncertain dynamic systems. The application of the qualitative-quantitative simulation is shown in this paper. The important question about the stability of a quanlitatively described dynamical system is solved by a novel analytic method.