Biomedical subjects

N M Bass

Publications and source records attributed to N M Bass.

132 records · Page 8Linked to original sources

PubMedDate not supplied

Radioimmunoassay of human ligandin.

A sensitive and specific radioimmunoassay for human ligandin has been developed and used to study ligandin release into the serum in acute and chronic hepatitis. Serum ligandin concentrations were elevated in 67 of 68 cases of acute viral hepatitis. Ligandin levels frequently returned to normal within the first 2 weeks of illness. The rapid disappearance of ligandin preceded the return to normal of serum SGOT. In chronic active hepatitis, serum ligandin levels correlated significantly (p less than 0.01) with histologic severity of disease. This correlation was not seen with SGOT. Serum ligandin may be useful in monitoring progress and the need for therapy in chronic active hepatitis.

Aspartate Aminotransferases↗

PubMedDate not supplied

Fatty acid-binding protein expression in the liver: its regulation and relationship to the zonation of fatty acid metabolism.

Liver fatty acid-binding protein (L-FABP) is expressed in a declining gradient between the portal and central zones of the liver acinus. This paper discusses the results of experimental studies which address the questions: (a) What factors regulate L-FABP expression in liver and produce its acinar gradient? (b) What is the relationship between the acinar gradient of L-FABP and acinar gradients in the transport and metabolism of long-chain fatty acids? Both high-fat diets and clofibrate-treatment increase L-FABP proportionally at both extremes of the liver acinus and the small intestine, with preservation of the L-FABP gradient in both tissues. Female rats differ from males, however, in showing a greater hepatic abundance of L-FABP which is expressed almost equally throughout the acinus. Dietary studies show that L-FABP is induced with increased fatty acid flux derived from dietary fat but not from de novo hepatic fatty acid synthesis. Studies of the synthesis and utilization of fatty acids by hepatocytes isolated from the periportal and pericentral zones of the liver acinus suggest that the acinar gradient of L-FABP is not associated with differences in the intrinsic capacity of zone 1 and zone 3 hepatocytes to utilize or synthesize fatty acids. In addition, studies of the acinar uptake pattern of a fluorescent fatty acid derivative by isolated perfused livers indicate that the acinar distribution of L-FABP does not determine the pattern of fatty acid uptake in the intact acinus. Rather, the acinar gradient of L-FABP is most likely to represent a response to physiological conditions existing in the intact acinus which may include gradients in the flux of fatty acids, fatty acid metabolites and hormones.

Animals↗

PubMedDate not supplied

Mechanisms of regulation of liver fatty acid-binding protein.

Liver fatty acid-binding protein (L-FABP) expression is modulated by developmental, hormonal, dietary, and pharmacological factors. The most pronounced induction is seen after treatment with peroxisome proliferators, which induce L-FABP coordinately with microsomal cytochrome P-450 4A1 and the enzymes of peroxisomal fatty acid beta-oxidation. These effects of peroxisome proliferators may be mediated by a receptor which has been shown to be activated by peroxisome proliferators in mammalian cell transfection studies. However, the peroxisome proliferators tested thus far do not bind to this receptor, known as the peroxisome proliferator-activated receptor (PPAR), and its endogenous ligand(s) also remain unknown. Peroxisome proliferators inhibit mitochondrial beta-oxidation, and one hypothesis is that the dicarboxylic fatty acid metabolites of accumulated LCFA, formed via the P-450 4A1 omega-oxidation pathway, serve as primary inducers of L-FABP and peroxisomal beta-oxidation. We have tested this hypothesis in primary hepatocyte cultures exposed to clofibrate (CF). Inhibition of P-450 4A1 markedly diminished, via a pre-translational mechanism, the CF induction of L-FABP and peroxisomal beta-oxidation. In further experiments, long-chain dicarboxylic acids, the final products of the P-450 4A1 omega-oxidation pathway, but not LCFA, induced L-FABP and peroxisomal beta-oxidation pre-translationally. These results suggest a role, in part, for long-chain dicarboxylic acids in mediating the peroxisome proliferator induction of L-FABP and peroxisomal beta-oxidation. We also found that LCFA, which undergo rapid hepatocellular metabolism, could become inducers of L-FABP and peroxisomal beta-oxidation under conditions where their metabolism was inhibited.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Cellular binding proteins for fatty acids and retinoids: similar or specialized functions?

The cellular fatty acid-binding proteins (FABP) and cellular retinoid (retinol, retinoic acid)-binding proteins (CRtBP) are structurally and functionally-defined groups within an evolutionarily conserved gene family. CRtBP are expressed in both fully differentiated and developing tissues in a manner that supports a relationship to the action of retinoic acid in morphogenesis and cellular differentiation. The FABP are, by contrast, expressed only in fully differentiated tissues in a manner compatible with a major function in the metabolism of long-chain fatty acids (LCFA) for energy production or storage. The precise function(s) of FABP and CRtBP remain imperfectly understood, while subspecialization of function(s) within the two groups is suggested by the complex diversity in both of structurally distinct members that display striking tissue and temporal specificity of expression in addition to ligand specificity. Notwithstanding this considerable apparent functional diversity among the FABP and CRtBP, available evidence supports a dual set of generic functions for both protein groups in a) promoting cellular flux of poorly water-soluble ligands and their subsequent metabolic utilization or transformation, and b) sequestration of ligands in a manner that limits their association with alternative binding sites within the cell, of which members of the steroid hormone nuclear receptor superfamily (HNR) are a potentially important category. Theoretical as well as experimental models probing diffusional fluxes of LCFA in vitro and in living cells have provided support for a function for FABP in intracellular LCFA transport. Protein-bound ligand also appears to provide the substrate for metabolic transformation of retinoids bound to CRtBP, but convincing evidence is lacking for an analogous mechanism in the direct facilitation of fatty acid utilization by FABP. An emerging relationship between FABP and CRtBP function centers on their binding of, and induction by, ligands which activate or transform specific HNR-the retinoic acid receptors and the peroxisome proliferator activated receptor in the case of CRtBP and FABP, respectively. Evidence consistent with both a 'promotive' role (provision of ligands for HNR) and a 'protective' role (limiting availability of free ligand for HNR association) has been advanced for CRtBP. Available data supports a 'protective' function for cellular retinoic acid-binding proteins (CRABP) and liver FABP (L-FABP) and points to the existence of ligand-defined, lipid-binding-protein-HNR relationships in which CRABP serve to attenuate the induction of gene expression by retinoic acid, and in which L-FABP may modulate a cellular adaptive multigene response to increased LCFA flux or compromised LCFA utilization.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMedDate not supplied

Is there any use for nontraditional or alternative therapies in patients with chronic liver disease?

There has been a substantial increase in the use of so-called complementary and alternative therapies by patients with liver disease. Although many such modalities are available, herbal therapies are the most popular, and of these remedies, silymarin extracted from the milk thistle is most widely subscribed to as a remedy for liver diseases. Available evidence points to a potential, but unproven, benefit for this as well as other therapies based on free radical scavenger or antioxidant principles in treating patients with liver disease. These therapies deserve further investigation through experimental studies and well-controlled clinical trials. Benefits to patients from these therapies, especially to patients with established cirrhosis, are most likely to be modest and insignificant. Conversely, the hepatotoxic potential of some alternative treatments is well recognized. As practitioners educating and treating patients with liver disease, we are obliged to be informed about popular alternative therapies, understanding of our patients' need to be partners in their care, and open-minded to the possibility that some benefit may come from some therapies currently regarded as alternative. We need to be effective and tolerant in learning about which alternative treatments our patients are taking, so that we can monitor their effects if any and counsel appropriately against those that may cause harm.

Animals↗

PubMedDate not supplied

The TMD series.

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Abbreviations as Topic↗