Fatty acid binding protein. Role in esterification of absorbed long chain fatty acid in rat intestine

Fatty acid binding protein (FABP) is a protein of 12,000 mol wt found in cytosol of intestinal mucosa and other tissues, which exhibits high affinity for long chain fatty acids. It has been suggested that FABP (which may comprise a group of closely related proteins of 12,000 mol wt) participates in cellular fatty acid transport and metabolism. Although earlier findings were consistent with this concept, the present studies were designed to examine its physiological function more directly. Everted jejunal sacs were incubated in mixed fatty acid-monoglyceride-bile acid micelles, in the presence or absence of equimolar concentrations of either of two compounds which inhibit oleate binding to FABP:flavaspidic acid-N-methyl-glucaminate and alpha-bromopalmitate. Oleate uptake, mucosal morphology, and oxidation of [14C]acetate remained unaffected by these agents, but oleate incorporation into triglyceride was inhibited by 62-64% after 4 min. The inhibition by flavaspidic acid was reversible with higher oleate concentrations. The effect of these compounds on enzymes of triglyceride biosynthesis was examined in intestinal microsomes. Neither flavaspidic acid nor alpha-bromopalmitate inhibited acyl CoA:monoglyceride acyl-transferase. Fatty acid:coenzyme A ligase activity was significantly enhanced in the presence of partially purified FABP, probably reflecting a physical effect on the fatty acid substrate or on the formation of the enzyme-substrate complex. Activity of the enzyme in the presence of 0.1 mM oleate was only modestly inhibited by equimolar flavaspidic acid and alpha-bromopalmitate, and this effect was blunted or prevented by FABP. We conclude that in everted gut sacs, inhibition of triglyceride synthesis by flavaspidic acid and alpha-bromopalmitate could not be explained as an effect on fatty acid uptake or on esterifying enzymes in the endoplasmic reticulum but rather can be interpreted as reflecting inhibition of fatty acid binding to FABP. These findings lend further support to the concept that FABP participates in cellular fatty acid transport and metabolism. It is also possible that FABP, by effecting an intracellular compartmentalization of fatty acids and acyl CoA, may play a broader role in cellular lipid metabolism.     

Evaluation of transbronchial biopsy of the lung

The histo-autoradiographic study of the subfornical organ by incorporation of 3H-Leucine in normal and dehydrated rats shows the existence of a protein synthesis; this synthesis is more important in dehydrated rats. Other studies are necessary to determine the nature and role of the substance synthetized.     

Effect of a high-beef diet on the fecal bacterial flora of humans

Ten human volunteers completed a 4-month diet series consisting of 1 month each of a control diet, a meatless diet, a high-beef diet, and the same control diet. Fat and fiber contents were essentially the same in all four diets, but protein content was doubled during the high-beef diet. During the 4th week on each diet, three stool specimens collected from each volunteer were analyzed for chemical composition and content of facultative, aerobic, and anaerobic bacteria. The bacteriological data are presented in this paper. High beef protein consumption had little effect on the composition of the intestinal flora. There were no significant differences in total counts of facultative and aerobic or anaerobic organisms in the feces when volunteers were on meatless or high-beef diets. At the species level, when counts during the two control diets were comparable, in only three instances did the change from the meatless to a high-beef diet significantly influence the bacterial numbers. The ratio of mean counts of anaerobic to facultative and aerobic organisms was approximately 15:1 during the meatless diet and 34:1 during the high-meat diet. The data indicate that animal protein consumption has little effect on the fecal bacterial profile in humans.     

Effect of dopamine on the esophageal smooth muscle in vivo

Using the method 133Xe clearance we investigated blood flow and calculated vascular resistances simultaneously in the muscles of the upper and lower extremities in 58 patients following successful surgical correction of aortic coarctation carried out at age 11.5 (+/- 2.9) years. The interval from operation to investigation was 11.5 (+/- 4.5) years. Resting and maximal ischemic exercise blood flows in the upper extremity were decreased and the duration of maximal blood flow was shortened. Values recorded from the lower extremities did not differ from normal controls. The difference between upper and lower extremities was statistically significant. Vascular resistance during maximal blood flow was higher in the upper extremities than in the lower. Differences between upper and lower extremities did not change after vasodilation elicited by amyl nitrite. The degree of differences was not dependent upon the age at operation, the age of the patients at investigation, or on the time interval between operation and investigation.     

NMR evidence against covalent attachment of an aldehyde ''transition-state'' analogue to alpha-chymotrypsin

The growth responses of an acetate-utilizing isolate of Butyrivibrio fibrisolvens to CO2, acetate and pyruvate were determined using a chemically-defined medium. Carbon dioxide was essential for growth and both acetate and pyruvate increased growth. 14C from [I-14C]pyruvate appeared predominantly in formate and lactate. These results, together with those obtained with enzyme preparations, indicated pyruvate synthase, pyruvate-CO2 exchange and pyruvate formate lyase to be active.     

Results of high-dose thoracic irradiation incorporating beam's eye view display in non-small cell lung cancer: a retrospective multivariate analysis

PURPOSE: To review the University of Michigan clinical experience in nonsmall cell lung cancer using high-dose thoracic irradiation (> or = 60 Gy) so that a starting dose for our prospective dose-escalation study could be determined. METHODS AND MATERIALS: Eighty-eight consecutive patients diagnosed with medically inoperable or locally advanced, unresectable nonsmall cell lung cancer were identified who were treated with thoracic irradiation alone to a minimum total dose of 60 Gy (uncorrected for lung density). All patients except four (95%) underwent computed tomography scanning for treatment planning that included beam's eye view display for tumor and critical structure localization. All patients were treated with standard fractionation in a continuous course to uncorrected total doses ranging from 60 to 74 Gy (median, 67.6 Gy). RESULTS: The median follow-up exceeds 24 months for all surviving patients (range, 12 to 78 months). The median survival time was 15 months, and the 2- and 3-year overall actuarial survival rates were 37% and 15%, respectively. Survival was significantly different between stage of disease (p = .004) and N-stage (p = .002) by univariate analysis. In a multivariate analysis, stage becomes the only characteristic significantly associated with outcome. The median time to local progression for 86 evaluable patients was 29 months. Stage (p = .0003), T-stage (p = .0095) and N-stage (p = .027) were significantly different with respect to local progression-free survival by univariate analysis. However, only stage was prognostic for local progression-free survival by multivariate analysis. There was no difference between large volume treatment (inclusion of the contralateral hilar and supraclavicular lymph nodes) and small volume treatment (exclusion of these elective nodal sites) with respect to local progression-free survival (p = .507) or survival (p = .520). With regard to dose, there was no significant difference between patients who received > 67.6 Gy and patients who received < or = 67.6 Gy with respect to local progression-free survival (p = .094) or survival (p = .142). Within the Stage III subgroup, local progression-free survival (p = .018) and survival (p = .061) were longer favoring the high-dose group of patients. Despite these doses, disease progression within the irradiated field was the predominant first site of treatment failure. CONCLUSION: This retrospective study has shown that it is feasible to deliver uncorrected tumor doses as high as 70 Gy using standard fractionation in NSCLC with acceptable morbidity. Local control remains a significant problem. These data indicate justification for a starting dose in a prospective radiation dose-escalation study.