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Biomedical subjects

N M Bass

Publications and source records attributed to N M Bass.

At least 19 recordsLinked to original sources
PubMed1995

Hepatic granulomas following liver transplantation. Clinicopathologic features in 42 patients.

Liver granulomas have long been known to pose diagnostic problems for pathologists; however, their prevalence and associated etiologic factors have not been studied in liver transplant patients. We reviewed 3632 liver biopsy specimens from 563 patients at two institutions and identified 42 patients with posttransplant granulomas. A possible or probable etiologic factor was identified in 30 (71%) cases. Most were epithelioid granulomas and microgranulomas located in the parenchyma associated with hepatocyte necrosis (21 cases, 50%). Portal-based granulomas were associated with recurrent primary biliary cirrhosis (5 cases, 12%), acute cellular rejection (2 cases, 4.8%), and a foreign body-type reaction (1 case, 2.4%). One case was associated with tuberculosis (2.4%), 4 cases occurred in a fatty liver (9.5%), and 8 patients had liver granulomas but no other significant abnormality. The granulomas were most frequent in the first 7 months after transplantation when the patients were biopsied more often and underwent episodes of rejection or acute hepatitis. Portal-based granulomas in this period were usually associated with acute cellular rejection. After 7 months, the frequency of granulomas as well as the number of biopsies decreased and portal-based granulomas associated with recurrent primary biliary cirrhosis were most common (5 cases, 12%). Rare, late-appearing parenchymal granulomas were also seen (3 cases) and consisted of 1 lipogranuloma and 2 cases of epithelioid granuloma. The latter were thought, in 1 patient, to be associated with parenchymal hepatocyte necrosis; the others were of unknown etiology.

Biopsy↗
PubMed1995

Expression of fatty acid binding protein in the liver during pregnancy and lactation in the rat.

Expression of the liver fatty acid binding protein (L-FABP) has been studied in the liver of pregnant and lactating rats. The L-FABP concentration found in the cytosol by immuno-enzymatic assay (ELISA) was consistently higher in the dams during the pregnancy and the lactation than in the age-matched virgin females. Paradoxically, a decrease in the L-FABP mRNA level occurred in the maternal liver during the last days of the gestation. This level remained low on days 7 and 14 of the lactation. Since the transcription rate of the L-FABP gene was unchanged in the maternal liver, these data suggest a post-transcriptional regulation of the L-FABP during pregnancy and lactation in the rat. The nutritional adaptations occurring during pregnancy and lactation are not involved in this regulation since a chronic maternal food-restriction failed to correct these modifications. The mechanism of this regulation is presently unknown, but possibilities include hormonally mediated effects.

Animals↗
PubMed1995

Transjugular intrahepatic portosystemic shunts for refractory ascites: assessment of clinical and hormonal response and renal function.

Cirrhosis is frequently complicated by ascites that may become resistant to diuretic therapy. Transjugular intrahepatic portosystemic shunts (TIPS) represent a new treatment for this debilitating condition. The aim of this study was to ascertain the clinical efficacy of TIPS, as well as its impact on renal function and on hormonal parameters. Five inpatients with refractory ascites were studied prospectively before TIPS, and 3 and 14 days after TIPS. After TIPS, ascites completely resolved or was minimal in all patients. Diuretics were discontinued in three subjects and decreased by at least 50% in two. One patient developed liver failure after TIPS and required liver transplantation; the others remained stable after a mean follow-up of 14 months. Mean urinary sodium excretion increased from 2.1 +/- 0.6 mEq/24 hr before TIPS to 13.0 +/- 4.3 mEq/24 hr 14 days after TIPS. Mean serum creatinine and glomerular filtration rate also tended to improve during the study period. With the exception of the patient who developed liver failure, plasma aldosterone concentration decreased from a mean of 126.0 +/- 29.9 ng/dL to 22.8 +/- 6.8 ng/dL (P = .04), and plasma renin activity decreased from a mean of 9.0 +/- 3.0 micrograms/L/h to 0.9 +/- 0.1 microgram/L/h (P = .08). Additionally, 19 patients who underwent TIPS for refractory ascites outside of this protocol were followed prospectively for a mean of 282 days. Clinical improvement in ascites control was noted in 74%, and the mean dose of diuretics was decreased by more than 50%. Nonresponders more often had underlying renal disease. In conclusion, TIPS is an effective therapy for refractory ascites in most patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Immunological identity of rat liver cytosolic heme-binding protein with purified and recombinant liver fatty acid binding protein by western blots of two-dimensional gels.

We examined the degree of similarity between rat liver cytosolic heme-binding protein (HBP) and rat liver fatty acid binding protein (L-FABP) purified from rat liver cytosol and recombinant L-FABP (rL-FABP). We compared 1) HBP, 2) L-FABP, and 3) rL-FABP prepared in three different laboratories and probed them with three different antisera also from different laboratories on Western blots. The objective was to determine whether the isoform pattern of the recombinant would resemble those of the purified rat liver proteins and whether heme is bound by the isoforms. To investigate the similarities, we compared the immunoreactivity of purified HBP, L-FABP, and rL-FABP by probing Western blots of 2-D gels with polyclonal antibodies raised against each of these proteins. All of the antibodies react with the same isoelectric species for each of the proteins. In addition, [55Fe]-heme binds equally well to the 2 major HBP isoforms.

Animals↗
PubMed1994

Evidence for a novel keratinocyte fatty acid uptake mechanism with preference for linoleic acid: comparison of oleic and linoleic acid uptake by cultured human keratinocytes, fibroblasts and a human hepatoma cell line.

Keratinocytes require the essential fatty acid (FA), linoleic acid (LA), for the synthesis of stratum corneum membrane lipids. A plasma membrane-FA binding protein (PM-FABP), is postulated to mediate cellular FA-uptake in hepatocytes and several other tissues, but the mechanism whereby exogenous FA are taken up by keratinocytes has not been investigated. This study examines the uptake of LA and oleic acid (non-essential) in cultured human keratinocytes, in comparison to dermal fibroblasts and the human hepatoma cell line, HepG2. As previously reported for hepatocytes, FA-uptake in keratinocytes was curvilinear, with an initial (30 s) rapid cellular influx. The initial uptake component was temperature dependent, exhibited saturable kinetics and was significantly inhibited by pretreatment with trypsin. In contrast, fibroblast FA-uptake lacked an initial rapid uptake component, was relatively temperature insensitive, and was not inhibited by trypsin. Keratinocytes differed from both hepatocytes and fibroblasts by more rapid uptake of LA in comparison to oleic acid during the initial influx phase. Moreover, FA-uptake in keratinocytes was not inhibited by preincubation with a anti-rat liver PM-FABP antibody. These data provide evidence for a PM-FA transporter in keratinocytes that is distinct from the hepatic PM-FABP. The apparent preference of the putative keratinocyte FA transporter for LA may function to ensure epidermal capture of sufficient LA for barrier lipid synthesis.

Adult↗
PubMed1992

The primary structure of fatty-acid-binding protein from nurse shark liver. Structural and evolutionary relationship to the mammalian fatty-acid-binding protein family.

The primary structure of a fatty-acid-binding protein (FABP) isolated from the liver of the nurse shark (Ginglymostoma cirratum) was determined by high-performance tandem mass spectrometry (employing multichannel array detection) and Edman degradation. Shark liver FABP consists of 132 amino acids with an acetylated N-terminal valine. The chemical molecular mass of the intact protein determined by electrospray ionization mass spectrometry (Mr = 15124 +/- 2.5) was in good agreement with that calculated from the amino acid sequence (Mr = 15121.3). The amino acid sequence of shark liver FABP displays significantly greater similarity to the FABP expressed in mammalian heart, peripheral nerve myelin and adipose tissue (61-53% sequence similarity) than to the FABP expressed in mammalian liver (22% similarity). Phylogenetic trees derived from the comparison of the shark liver FABP amino acid sequence with the members of the mammalian fatty-acid/retinoid-binding protein gene family indicate the initial divergence of an ancestral gene into two major subfamilies: one comprising the genes for mammalian liver FABP and gastrotropin, the other comprising the genes for mammalian cellular retinol-binding proteins I and II, cellular retinoic-acid-binding protein myelin P2 protein, adipocyte FABP, heart FABP and shark liver FABP, the latter having diverged from the ancestral gene that ultimately gave rise to the present day mammalian heart-FABP, adipocyte FABP and myelin P2 protein sequences. The sequence for intestinal FABP from the rat could be assigned to either subfamily, depending on the approach used for phylogenetic tree construction, but clearly diverged at a relatively early evolutionary time point. Indeed, sequences proximately ancestral or closely related to mammalian intestinal FABP, liver FABP, gastrotropin and the retinoid-binding group of proteins appear to have arisen prior to the divergence of shark liver FABP and should therefore also be present in elasmobranchs. The presence in shark liver of an FABP which differs substantially in primary structure from mammalian liver FABP, while being closely related to the FABP expressed in mammalian heart muscle, peripheral nerve myelin and adipocytes, opens a further dimension regarding the question of the existence of structure-dependent and tissue-specific specialization of FABP function in lipid metabolism.

Amino Acid Sequence↗
PubMed1992

Mechanism-based probes of the topology and function of fatty acid hydroxylases.

The use of three mechanism-based probes to investigate the topology and function of fatty acid hydroxylases is discussed. 1) The observation of protein rather than heme alkylation in the reaction of cytochrome P4504A1 with 10-undecynoic acid supports the argument that the enzyme circumvents the inherent preference for omega-1 hydroxylation by restricting access to the ferryl oxygen. 2) The regiochemistry of the ferricyanide-mediated iron-to-nitrogen shift of the cytochrome P450102 (P450BM-3) phenyl-iron complex indicates that the active site of this bacterial fatty acid hydroxylase is open primarily above pyrrole ring A of the prosthetic heme group, 3) Inhibition of clofibrate-mediated peroxisome proliferation in cultured rat hepatocytes by inactivation of cytochrome P4504A1 indicates that omega-hydroxylation of fatty acids provides a signal for peroxisome proliferation.

Animals↗
PubMed1992

Intracranial pressure monitoring and liver transplantation for fulminant hepatic failure.

Cerebral edema and intracranial hypertension, commonly present in fulminant hepatic failure, may lead to brainstem herniation and limit the survival of comatose patients awaiting liver transplantation before a donor organ becomes available. Also, they are likely responsible for postoperative neurological morbidity and mortality. Although intracranial pressure monitoring has been proposed to aid clinical decision making in this setting, its use in the prevention of brainstem herniation preoperatively, in the selection of patients for liver transplantation who have the potential for neurological recovery and in the maintenance of cerebral perfusion during liver transplantation has not been examined in detail. To address these issues, we established a protocol for intracranial pressure monitoring in comatose patients with fulminant hepatic failure as part of their preoperative and intraoperative management. Twenty adults and three children underwent intracranial pressure monitoring. Ten patients required preoperative medical therapy with mannitol, barbiturates or both for a rise in intracranial pressure above 25 mm Hg. Four patients had a sustained lowering of intracranial pressure, three of whom survived hospitalization. Six patients had intracranial hypertension refractory to medical management, were removed from a waiting list for a donor organ and died with brainstem herniation. Of the remaining 17 patients, 3 died of other causes while awaiting a donor organ, 2 recovered spontaneously without neurological sequelae and 12 underwent liver transplantation. All but one patient undergoing liver transplantation had transient intraoperative intracranial hypertension develop, requiring medical treatment. The 12 patients who had transplants recovered neurologically and were discharged from the hospital.(ABSTRACT TRUNCATED AT 250 WORDS)

Hepatic Encephalopathy↗
PubMed1991

In situ binding of fatty acids to the liver fatty acid binding protein: analysis using 3-[125I]iodo-4-azido-N-hexadecylsalicylamide.

A photoactivatable radioiodinated fatty acid analogue, 3-[125I]iodo-4-azido-N-hexadecylsalicylamide (125I-AHS) has been synthesized and used to investigate the involvement of cellular lipid carriers in hepatic fatty acid utilization. Photoactivation of Hep G2 internalized 125I-AHS revealed that several cellular proteins were crosslinked with the radiolabeled fatty acid analogue. Three predominant proteins in the membrane fraction of the cell with molecular masses 17, 50 and 127 kDa were crosslinked with the lipid analogue, as determined using autoradiography after SDS-PAGE. Three other proteins in the soluble fraction of the cell, with molecular masses 14, 24 and 35 kDa, were also labeled in situ. In contrast to the other labeled proteins, the fatty acid analogue accumulated on the cytoplasmic 14 kDa protein in a time and temperature dependent fashion. The in situ-labeled 14 kDa protein was identified from primary rat hepatocytes as the liver fatty acid binding protein by partial purification and its ability to be immunoprecipitated with immunospecific L-FABP antiserum. Collectively the results indicate that fatty acids traverse the plasma membrane and are bound cytoplasmically by the liver fatty acid binding protein, as well as other proteins in the cell. This represents the first demonstration in intact hepatocytes that the liver fatty acid binding protein participates in the process of intracellular fatty acid trafficking, and supports a model in which cytoplasmic lipid carriers solubilize fatty acids as a step in their metabolic utilization.

Affinity Labels↗
PubMed1991

A methylsulfonyl metabolite of a polychlorinated biphenyl can serve as a ligand for liver fatty acid binding protein in rat intestinal mucosa.

When a 100,000 x g supernatant from rat intestinal mucosa was incubated with 4,4'-bis([3H]methylsulfonyl)-2,2',5,5'-tetrachlorobiphenyl, [(CT3SO2)2TCB] a (CT3SO2)2TCB-protein complex was formed. The (CT3SO2)2TCB-protein complex was isolated and purified using gel filtration and ion-exchange chromatography. The protein portion of this complex was characterized to be liver fatty acid binding protein (L-FABP) by SDS-polyacrylamide gel electrophoresis and immunoblot analysis. No cross reactivity was observed in the immunoblot analysis between the purified protein and anti-heart or anti-intestinal fatty acid binding protein. (CT3SO2)2TCB was extractable from L-FABP and therefore not covalently bound to L-FABP.

Animals↗
PubMed1991

Isolation and characterization of fatty acid binding protein in the liver of the nurse shark, Ginglymostoma cirratum.

1. A 14.5 kDa fatty acid binding protein was isolated from the liver of the nurse shark, Ginglymostoma cirratum. 2. Purified shark liver FABP (pI = 5.4) bound oleic acid at a single site with an affinity similar to that of mammalian FABP. 3. The apparent size, pI and amino acid composition of shark liver FABP indicate a close structural relationship between this protein and mammalian heart FABP.

Animals↗
PubMed1991

The aesthetic analysis of the face.

An analysis of the facial soft tissues is presented which permits aesthetic considerations of facial harmony and balance to be measured, and assessed quantitatively. The assessment is carried out in a practical and straight-forward manner, avoiding the measurement of angles. The visually determined Aesthetic Horizontal Line is used as the reference line, with more reliability than the Natural Head Position and more relevance to the soft tissues than Frankfort Horizontal. The analysis accurately predicts the correct position of the mandible so that the extent of orthopaedic or surgical correction necessary can be evaluated. The ideal position and angulation of the maxillary incisors are determined and established as treatment goals, to give optimal exposure of the dentition in expressive behaviour. Comparison of before and after treatment cephalograms permits quantitative assessment of aesthetic change.

Adolescent↗
PubMed1991

Hepatic transport of a fluorescent stearate derivative: electrochemical driving forces in intact rat liver.

We determined the effect of varying the transmembrane Na+ electrochemical gradient on extraction of a fluorescent derivative of stearate, 12-N-methyl-7-nitrobenzo-2-oxa-1,3,-diazol-amino stearate (NBD-stearate), by the isolated perfused rat liver. Membrane potential difference (PD) of individual hepatocytes and extraction of NBD-stearate were measured simultaneously under basal conditions and during changes in PD induced by perfusate ion substitutions. Under basal conditions, PD average -30 +/- 1 mV, and extraction of 10 microM NBD-stearate from 1% albumin solutions averaged 0.54 +/- 0.03. Fluorescence microscopy indicated that uptake exhibited a declining portal-to-central gradient in the presence but not absence of Na+. Substitution of nitrate for Cl- hyperpolarized PD to -59 mV and increased extraction to 131% of control values. Withdrawal of nitrate and substitution of gluconate for Cl- depolarized PD to -3 and -15 mV, respectively, and decreased extraction to 63 and 73% of control values. Substitution of choline for Na+ eliminated the out-to-in Na+ gradient, depolarized PD to -16 mV, and decreased extraction to 27% of control values, an effect greater than expected for membrane depolarization alone. Uptake of NBD-stearate was saturable and caused Na(+)-dependent membrane depolarization at higher concentrations (300 microM). These studies indicate that uptake of NBD-stearate occurs in large part by an efficient Na(+)-dependent mechanism compatible with electrogenic Na(+)-fatty acid cotransport.

4-Chloro-7-nitrobenzofurazan↗