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.     

Circulatory changes during anesthetic induction: impact of d-tubocurarine pretreatment, thiamylal, succinylcholine, laryngoscopy, and tracheal lidocaine

Circulatory changes after IV d-tubocurarine (3 mg), thiamylal (4 mg/kg) plus succinylcholine (2 mg/kg) and followed by direct laryngoscopy with or without intratracheal lidocaine spray (2 mg/kg) just before endotracheal intubation (EI), were measured in 40 adult patients. Pretreatment with d-tubocurarine did not alter mean arterial pressure (MAP), heart rate (HR), or central venous pressure (CVP). One minute after thiamylal-succinylcholine and just before laryngoscopy, MAP was 15 torr less than the awake value (p less than 0.05) and HR was 13 beats/min greater than the awake value (p less than 0.05). Laryngoscopy and EI elevated MAP above awake levels and further increased HR in all patients. The magnitude of these responses immediately following EI was not altered by tracheal lidocaine. However, the pressor and HR changes following EI were more transient when tracheal lidocaine was used (20 patients) and these patients were more likely to tolerate the tracheal tube without immediate additional anesthesia. The incidence of ventricular dysrhythmias was not altered by tracheal lidocaine. Compared with awake values, the cardiac index did not change significantly following intubation but stroke volume was decreased (p less than 0.05), with or without tracheal lidocaine.     

Serial measurement of arterial plasma progesterone levels throughout gestation and parturition in individual rats

Daily blood samples were taken from 6, chronically cannulated, fully conscious rats to measure plasma progesterone levels throughout gestation. Progesterone levels in individual rats fluctuated by up to 28 ng/ml per day, but tended to be consistently higher or lower than the group mean. The accuracy of predicting progesterone levels in individual rats from previous values was examined. Progesterone levels on day 7 of gestation were negatively correlated with foetal weights near term. There was little indication that high progesterone levels at any stage of gestation lead to increased foetal or placental weights. Progesterone levels on day 17 were positively correlated with the number of corpura lutea but there was little relationship between progesterone and either the number or total mass of the placentas. Serial blood samples taken from a second group of 6 rats at 2 hourly intervals showed that the time between the major fall in progesterone levels to below 12 ng/ml and the onset of parturition was relatively constant (varying by only 8 h) despite a 29 h range in the total length of gestation.     

Reovirus-specific polypeptides: analysis using discontinuous gel electrophoresis

An analysis of reovirus-specific polypeptides in cells infected with temperature-sensitive mutants under permissive and nonpermissive conditions revealed the presence of (i) all the known viral polypeptides and (ii) aberrant migration of the mu 1 and mu 2 polypeptides in four groups of mutants.     

The effect of vasectomy on pituitary-gonadal function in men

The testosterone concentration in allantoic fluid between 90 and 150 days of gestation in cattle can be used to determine the fetal sex; values were 442 +/- 20-3 (S.E.M.) pg testosterone/ml for males fetuses and 215 +/- 8-2 pg/ml for female fetuses.     

Morphometric analysis of rat hepatocytes after total billary obstruction

Using light and electron microscopic morphometric techniques, the effects of 48 hr of extrahepatic biliary obstruction on hepatocyte structure were examined in the rat. Liver cells near the portal area were compared to those in the centrilobular regions of the hepatic lobule. Observations on the normal animals confirm earlier evidence of quantitative differences in the surface density of organelles in hepatocytes located within different regions of the lobule. A striking difference in the quantity of the Golgi complex in the two areas of the lobule was noted for the first time, with the portal cells containing a significantly greater quantity of this organelle than centrolobular hepatocytes. After 48 hr of total obstruction, most of the previously reported qualitative changes in the canalicular and pericanalicular regions were confirmed. Morphometric analysis at the light-microscopic level showed an increase in the number of cells and a decrease in cell size in those cells near the portal area were compared to those in the centrolobular regions of the helar level demonstrated a significant decrease in both rough and smooth surfaced endoplasmic reticulum in cells of both zones, a finding in marked contrast to the hypertrophy of smooth endoplasmic reticulum suggested by other investigators on the basis of qualitative assessments. There was also a striking decrease in the amount of the Golgi complex, limited to cells in the portal regions. In addition, in all zones a decrease in the volume density of mitochondria and lysosomes was noted, whereas the volume of microbodies was increased. It is suggested that this loss in total membrane material within the cell may be secondary to the degranulation and decrease in total surface area of rough surfaced endoplasmic reticulum, an organelle thought to be responsible in part for the synthesis of new cellular membranes. These observations suggest that present concepts concerning the pathogenesis of cholestatic liver disease require reappraisal.     

Tracheal obstruction associated with a fungus ball. A case of primary tracheal candidiasis

A case of transient filling defects in the renal pelves and ureters, secondary to spontaneously occurring acquired anticoagulants, is presented. The relationship of this entity to hemophilia, immunologic disorders, such as systemic lupus erythematosis, and normal post partum patients is discussed. The differential diagnosis for filling defects in the renal pelvis is reviewed.     

The potential of the teaching hospital for the development of prepaid group practices

This paper deals with the development of a hospital based prepaid group practice at Long Island Jewish-Hillside Medical Center. The paper provides an historical perspective of the factors leading to the decision to develop such a Medical Group practice, the difficulties encountered in obtaining conceptual approval from the Medical Center's Board of Trustees and its medical staff, the negotiations between the Medical Center and Blue Cross-Blue Shield of Greater New York as the insurance company which agreed to market the program and to subsidize it in its developmental stage, factors relating to the contractual negotiations between the Medical Center and Blue Cross, the key elements of the negotiated contract from the standpoint of the prepaid group, and the nature of the subsidies provided to ensure a healthy fiscal beginning. The paper highlights the methods used in achieving the desired goals and the development of the Group, sets forth the resistance which other, similar hospitals might anticipate in undertaking such a venture of their own, and highlights the nature and the degree of commitment necessary to bring such a program into being.