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Biomedical subjects

N M Bass

Publications and source records attributed to N M Bass.

At least 109 records · Page 6Linked to original sources

Sterol carrier protein 2 and fatty acid-binding protein. Separate and distinct physiological functions.

Sterol carrier protein 2 (SCP-2) participates in the microsomal conversion of lanosterol to cholesterol, in the conversion of cholesterol to cholesterol ester, and in intracellular cholesterol transfers. The stoichiometry of binding between cholesterol and SCP-2 is 1:1. However, reports have appeared attributing sterol carrier protein activity to a protein preparation identical to hepatic fatty acid-binding protein (FABP). Therefore, the present investigation was conducted to compare homogeneous preparations of FABP and SCP-2 with respect to their capacities to participate as carrier proteins in reactions involving sterols or fatty acids. The results show that SCP-2 and FABP have separate and distinct physiological functions, with SCP-2 participating in reactions involving sterols and FABP participating in reactions involving fatty acid binding and/or transport. Furthermore, there is no overlap in substrate specificities, i.e. FABP does not possess sterol carrier protein activity and SCP-2 does not specifically bind or transport fatty acid. As long as only small quantities of organic solvent (1.6 volume %) were used for substrate addition, the sterol delta 7-reductase liver microsomal assay for SCP-2 correlated well with the physiologically relevant assays employed in the reconstituted adrenal system. The sterol carrier protein activity previously attributed to rat hepatic FABP is explained by the presence of significant quantities of propylene glycol (15 volume %) or Tween 80 in the assay procedure.

Adrenal Glands↗

Regulation of the biosynthesis of two distinct fatty acid-binding proteins in rat liver and intestine. Influences of sex difference and of clofibrate.

Two distinct fatty acid-binding proteins (FABPs) have been identified in rat intestine, gFABP (15,063 Da) which is confined to intestinal epithelium and hFABP (14,184 Da) which is found in both liver and intestine. We have examined the influence of sex difference and the effect of clofibrate, both of which affect cellular fatty acid metabolism and hFABP levels, on the concentration, and mRNA levels of both hepatic and intestinal FABPs. In the liver, hFABP concentration was approximately 2-fold greater in females and in clofibrate-treated males than in untreated male rats. These differences were not accompanied by changes in the fractional turnover of the polypeptide but rather by parallel increases in hFABP mRNA. In the intestine, the two FABPs exhibited different regulatory responses. Intestinal hFABP turnover was 33% greater in females than in males, whereas mRNA concentration was 50% greater. Thus, unlike hFABP in liver, there was no sex-related difference in the steady-state level of hFABP in intestine. However, clofibrate treatment, similar to its effects in the liver, doubled intestinal hFABP protein and mRNA concentration. In contrast to hFABP, neither gFABP protein nor mRNA concentration were sex dependent, whereas clofibrate produced only a modest increase in gFABP concentration without significantly changing gFABP mRNA levels. The results indicate that the influence of sex difference and the effect of clofibrate on hepatic fatty acid metabolism are both associated with changes in hFABP synthesis mediated pretranslationally. The differential response of hFABP and gFABP in intestine suggests that these proteins play distinct roles in the cellular metabolism of fatty acids.

Animals↗

Magnetic resonance imaging and spectroscopy of hepatic iron overload.

Experimental animals that had been given excess iron in their diet were studied by magnetic resonance (MR) imaging in vivo and by magnetic resonance (MR) spectroscopy in vitro. Hepatic iron overload in patients with transfusional iron excess was studied by MR imaging, and isolated iron protein fractions were studied in vitro by MR spectroscopy. The spin echo image intensity of livers with iron overload was decreased because of the extreme decreases in T2 compared with normal; T1 was decreased only moderately. The relaxation rates 1/T2 and 1/T1 both showed a linear relationship to hepatic iron levels. Ferritin solutions showed moderate decreases in T2 and mild decreases in T1. The T2 relaxivity of ferritin, which is due to the iron core rather than the apoferritin protein shell, does not appear sufficient to account for the extreme decrease in T2 observed in hepatic iron overload. Low molecular weight cytosol iron is present in lower concentrations than ferritin but potentially has much greater relaxivity and may contribute to the MR findings. These techniques may be useful in other studies of iron metabolism.

Adolescent↗

Partial purification of molecular weight 12 000 fatty acid binding proteins from rat brain and their effect on synaptosomal Na+-dependent amino acid uptake.

High-affinity, Na+-dependent synaptosomal amino acid uptake systems are strongly stimulated by proteins which are known to bind fatty acids, including the Mr 12 000 fatty acid binding protein (FABP) from liver. To explore the possibility that such a function might be served by fatty acid binding proteins intrinsic to brain, we examined the 105000g supernatant of brain for fatty acid binding. Observed binding was accounted for mainly by components excluded by Sephadex G-50, and to a small degree by the Mr 12 000 protein fraction (brain FABP fraction). The partially purified brain FABP fraction contained a protein immunologically identical with liver FABP as well as a FABP electrophoretically distinct from liver FABP. Brain FABP fraction markedly stimulated synaptosomal Na+-dependent, but not Na+-independent, amino acid uptake, and also completely reversed the inhibition of synaptosomal Na+-dependent amino acid uptake induced by oleic acid. Palmitic, stearic, and oleic acids were endogenously associated with the brain FABP fraction. These data are consistent with the hypothesis that Mr 12 000 soluble FABPs intrinsic to brain may act as regulators of synaptosomal Na+-dependent amino acid uptake by sequestering free fatty acids which inhibit this process.

Amino Acids↗

Ligandin concentrations in the steroidogenic tissues of the rat during development.

Ligandin, a ubiquitous multifunctional cytoplasmic protein which exhibits glutathione S-transferase, glutathione peroxidase and delta 5-3-ketosteroid isomerase activities and binds to cortisol metabolites, is present in relatively high concentrations in gonadal and adrenal tissue. In contrast to hepatic ligandin, little is known about the ontogeny of ligandin in steroid-synthesising tissues. We report here the intracellular concentrations of ligandin as well as the serum concentrations of testosterone and progesterone measured by radioimmunoassay at different stages of development in the rat. Ligandin levels in testis, ovary and adrenal tissue were relatively high soon after birth, decreased by day 9 and increased rapidly during puberty to reach adult levels. These changes appeared to be paralleled by changes in the circulating levels of testosterone and progesterone. In contrast, ligandin levels in non-steroidogenically active tissues, such as liver and kidney, were low at birth and rose progressively to reach adult levels. Whereas hepatic ligandin concentration could be increased at all stages of development by phenobarbital induction, no induction occurred in the endocrine tissues.

Adrenal Glands↗

Cloning of a cDNA encoding rat intestinal fatty acid binding protein.

Intestinal fatty acid binding protein mRNA is one of the most abundant mRNA species in the rat small intestinal epithelium. RNA transfer blot analyses disclosed that the mRNA encoding intestinal fatty acid binding protein is approximately equal to 900 nucleotides long and not represented in liver RNA. We have identified 564 nucleotides of this mRNA, including 12 nucleotides of the 5' nontranslated region, the coding portion, and 155 nucleotides of the 3' nontranslated domain. The primary translation product encoded by this mRNA contains 132 amino acids and has a Mr of 15,062. The derived protein sequence was verified by automated sequential Edman degradation of the intact polypeptide isolated from a wheat germ cell-free system. The in vitro product is NH2-terminally acetylated, a finding that is consistent with its ultimate cytoplasmic destination. Comparison of the amino acid sequence of this protein with liver fatty acid binding protein, a polypeptide specified by the most abundant small intestinal epithelial mRNA, revealed significant homology and similarity in the predicted secondary structures of their NH2-terminal domains.

Amino Acid Sequence↗

Chronic liver disease: evaluation by magnetic resonance.

Magnetic resonance (MR) imaging distinguished hepatitis from fatty liver and cirrhosis in a woman with a history of alcohol abuse. Anatomic and physiologic manifestations of portal hypertension were also demonstrated by MR.

Adult↗

Orthopedic coordination of dentofacial development in skeletal Class II malocclusion in conjunction with edgewise therapy. Part II.

This second of two articles describes the effects of mandibular growth enhancement in a comprehensive orthopedic approach to the correction of skeletal Class II malocclusion. Clinical and experimental evidence gives support to the concept, and case histories show the clinical mode of use of the appliance system. An initial 10- to 12-month orthopedic phase is followed by a second phase of similar duration in which full edgewise therapy is used to establish a gnathologically ideal occlusion. As the essential corrections are achieved in the orthopedic phase, the second phase is much reduced in complexity and is generally confined to alignment and final detailing. This combined approach to skeletal Class II treatment offers the possibility of better harmony of dental and facial features, with continued stability through the period of facial growth.

Cephalometry↗

Orthopedic coordination of dentofacial development in skeletal Class II malocclusion in conjunction with edgewise therapy. Part I.

The skeletal Class II malocclusion may be considered to develop as a failure of the coordinating process to maintain harmonious relationships within the developing dentofacial apparatus. If the skeletal elements are too far apart for adaptation to occur and/or if there are functional abnormalities of the orofacial musculature which inhibit coordination from taking place, a malocclusion will result. An orthopedic technique and appliance system has been developed with the intention of improving those factors responsible for the development and perpetuation of the skeletal Class II malocclusion in a primary stage of treatment. This is accomplished by means of restraint and redirection of forward maxillary growth and an increase in the velocity of mandibular growth. Concurrently, adverse soft-tissue influences are eliminated or ameliorated. Edgewise appliance therapy is subsequently carried out for the final correction. The subject is considered in two articles. This first article describes the effects of the restraint of maxillary growth on craniofacial development and the dental changes produced by a maxillary removable splint with extraoral traction and shows how they can be used clinically for correction of the skeletal Class II malocclusion. The experimental and clinical evidence supporting this approach is considered, and case histories show the clinical use of the maxillary splint. This form of maxillary therapy for the skeletal Class II malocclusion has limitations, and it is desirable for it to be incorporated into a comprehensive orthopedic system.

Cephalometry↗

Randomised, controlled study of transhepatic obliteration of varices and oesophageal stapling transection in uncontrolled variceal haemorrhage.

Percutaneous transhepatic obliteration and surgical stapling transection of the oesophagus with the EEA gun were compared prospectively in the treatment of uncontrolled oesophageal variceal haemorrhage unresponsive to conservative measures. Twenty patients with cirrhosis, with a patient portal vein and who were considered suitable for general anaesthesia and surgery, were randomised to two treatment groups (10 patients each). Immediate arrest of haemorrhage was achieved in 17 patients (nine surgery, eight obliteration). In one other patient, stapling transection succeeded where attempted transhepatic obliteration failed, and in another patient obliteration succeeded where attempted transection had failed. One patient continued to bleed and died following attempts at both procedures. Two other patients also died in hospital, without rebleeding following surgery. Variceal rebleeding during the same hospital admission occurred in two patients in the obliteration group and in none after surgery. Oesophageal stapling transection compares very favourably with a non-surgical technique such as transhepatic obliteration of varices in the emergency treatment of uncontrolled variceal haemorrhage in patients with moderate liver failure.

Adult↗

Nuclear magnetic resonance imaging of experimentally induced liver disease.

Experimental animal models of hepatitis, fatty liver, and hepatic iron overload were evaluated using a 3.5-kGauss nuclear magnetic resonance (NMR) imaging system. Increases in image intensity measurements and in T2 relaxation times equalled the sensitivity of histologic findings for the detection of early stages of hepatitis. A significant shift in T1 relaxation times characterized the early stages of hepatic necrosis. Liver triglyceride content correlated significantly with increases in NMR intensity measurements (p less than 0.01); however, changes in liver water content had a much greater influence on intensity, T1, and T2. Thus, it may be possible to distinguish hepatitis from benign fatty liver. Liver iron content correlated with decreases in NMR intensity measurements (p less than 0.001), and iron levels as low as 1.2 mg/g were detected. NMR may more specifically identify hepatocellular iron overload than do other techniques that do not distinguish hepatocellular from reticuloendothelial iron.

Animals↗

Chronic intrahepatic cholestasis due to sarcoidosis.

Two West Indian patients with Kveim-biopsy proven sarcoidosis developed chronic cholestatic liver disease, clinically and biochemically similar to primary biliary cirrhosis. Liver histology revealed multiple granulomas with reduction in bile ducts and, in one patient, progression to biliary cirrhosis. Portal hypertension was present in both patients leading to severe variceal haemorrhage in one. Mitochondrial antibody was negative in both patients and when used in conjunction with the Kveim-Siltzbach skin test serves to differentiate chronic intrahepatic cholestasis secondary to sarcoidosis from primary biliary cirrhosis.

Biopsy↗

Dento-facial orthopaedics in the correction of class II malocclusion.

An orthopaedic appliance system has been developed with the specific therapeutic intention of removing those factors responsible for the initiation or maintenance of the skeletal Class II malocclusion. This is accomplished by means of restraint and redirection of forward maxillary growth and induction of mandibular growth. Concurrently, adverse soft tissue influences are eliminated or ameliorated. Clinical and experimental evidence gives support to this concept and case histories show that clinical mode of use of the appliance system. An initial 10--12 month orthopaedic phase is followed by a second phase of similar duration, utilizing full Edgewise therapy to perfect the occlusion. The second phase is much reduced in complexity and is generally confined to alignment and final detailing as the essential corrections have been achieved in the orthopaedic phase. It is considered that this combined approach to Skeletal II treatment is more physiologic than conventional treatment and results in a better harmony of dental and facial features.

Adolescent↗

Wilson's disease. Clinical correction with cranial computed tomography.

Cranial computed tomograms of 12 patients with proven Wilson's disease were correlated with clinical disturbances. CT abnormalities occurred only in the eight patients with neurological manifestations. The presence of atrophy and low density lesions of the basal ganglia shown on CT correlated well with clinical signs of extrapyramidal dysfunction. Cerebral atrophy and cerebellar cortical atrophy were only moderately related to the degree of intellectual dysfunction and ataxia, respectively; there were no specific clinical signs in cases with brainstem involvement. Abnormalities may be marked in scans taken within a year of neuropsychiatric symptoms, but the most severely abnormal CT scans occurred in patients with a relatively longer duration of untreated disease. Computed tomography provides the opportunity to follow the response of the abnormalities of the brain to cupruresis and can give some assistance in management.

Adolescent↗

Long-standing asymptomatic primary sclerosing cholangitis: report of three cases.

Three patients, two males and one female, with asymptomatic primary sclerosing cholangitis (PSC) are described. The diagnosis was made in each case by endoscopic retrograde cholangiography after investigation of persistent elevation of the serum alkaline phosphatase. All three have remained completely well without any medical or surgical treatment for 3, 7, and 15 years, respectively, despite extensive involvement of the biliary tree. Follow-up liver biopsies in two have shown no histological evidence of progression to secondary biliary cirrhosis. PSC may occur more frequently and may follow a less severe clinical course than previously recognized.

Adult↗

Immunohistological localization of ligandin in human tissues.

An immunohistochemical localization of ligandin was undertaken in formalin fixed and paraffin wax embedded human tissues using the indirect immunoperoxidase (PAP) method and a monospecific antiligandin serum raised in rabbits. A substance reacting with this antiligandin serum was distributed diffusely in normal liver and selectively in kidney, intestine, testis, ovary and adrenal cortex. Small changes in the distribution and intensity of the reaction product were found in inflammatory conditions such as hepatitis, cholestasis, pyelonephritis and renal allograft rejection. Tissues which normally appear to contain abundant ligandin produce, as a general rule, easily demonstrate amounts of antiligandin reacting substance in the tumors and hyperplasias which arise from them.

Adrenal Cortex↗