Biomedical subjects
Publications and source records attributed to A Moser.
The case of a 21-year-old man with obstructive hydrocephalus who suffered multiple shunt failures is presented. The patient developed a syndrome of akinetic mutism that improved after administration of bromocriptine and metoprolol.
The effect of a lipid emulsion containing long-chain triglycerides (LCT) and supplemented with L-carnitine on plasma lipids and bilirubin in premature neonates on total parenteral nutrition was compared to that of lipid emulsions containing either LCT or a mixture of LCT and medium-chain triglycerides (MCT). In a double-blind randomized study 49 premature neonates received one of the three fat emulsions, given intravenously, over 16-20 h daily for 6 days. Plasma carnitine levels increased significantly in the supplemented group only; the addition of carnitine did not seem to affect any of the parameters studied. Mean plasma triglycerides rose by 193 and 199% in the carnitine-supplemented and the LCT groups, respectively, and by 314% in the MCT/LCT group. On the sixth day of the study free fatty acids were significantly higher in the MCT/LCT group than in the other two groups. Plasma phospholipids and free cholesterol increased (p < 0.05) progressively in all groups and were correlated (r = 0.74, p < 0.001). At the end of the 6-day study all groups showed a similar decline in free and total bilirubin levels despite the significant increase in plasma lipids and free fatty acids resulting from the stepwise increase in lipid load. No correlation was found between free fatty acids and free bilirubin. Since hyperbilirubinemia and hypertriglyceridemia appear to be clinically independent factors, the infusion of lipids should not be withheld from jaundiced infants on total parenteral nutrition.
The effects of an intravenously administered lipid emulsion supplemented with gamma-linolenic acid on the fatty acid profile of premature infants were compared with those of two conventional lipid emulsions. Fifty-nine premature neonates receiving total parenteral nutrition were randomly assigned to receive either fat emulsion containing gamma-linolenic acid and long-chain triglycerides (LCT), an LCT emulsion, or a 50% (wt/wt) mixture of medium-chain triglycerides and LCT emulsion. Forty-nine infants completed the study. During the 6-day study there was a significant tenfold increase in the plasma levels of gamma-linoleic acid in the supplemented group versus the other two groups. A significant threefold to fivefold increase in the omega 6 long-chain polyunsaturated fatty acids was observed in all groups. These changes seemed to be attributable mostly to linoleic acid from the lipid emulsion, despite the 50% lower dose in the medium- and long-chain triglycerides group. The increase in the omega 3 long-chain polyunsaturated fatty acids also was mainly caused by a similar increase in the level of alpha-linolenic acid. No differences were recorded in the linoleic/alpha-linolenic acid ratio among the groups. Plasma levels of some of the semiessential fatty acids were significantly higher in the medium- and long-chain triglycerides group than in the LCT group. This may be related to slower elimination of LCT, to the difference between emulsions, or to less substrate inhibition on delta-6-desaturase, which seems to be less of a rate-limiting enzyme than previously considered. Further intravenous feeding trials are needed to identify the optimal balance of fatty acids for nutrition of these premature infants.
Iatrogenic injury of the recurrent laryngeal nerve is doubtless one of the main problems in thyroid surgery. 56 consecutive patients, which have undergone surgical treatment for thyroid disease over the past two years are analysed. The recurrent laryngeal nerve is routinely exposed during thyroid surgery in order to decrease the incidence of recurrent nerve lesions. Four patients had an unilateral paralysis prior to the operation. Six patients showed a paralysis after the surgical intervention, two of whom had a carcinoma, where the nerve had to be resected. The residual four cases had only a transitory functional loss of one vocal cord which recovered within two weeks. We are convinced that the incidence of permanent nerve injury can be greatly decreased by exposure of th recurrent laryngeal nerve during thyroid surgery.
A 26-year-old patient presented with epigastric pain of sudden onset and severe puffy swelling of both legs and forearms. An irregularly shaped nodular filling defect on selective jejunal films, severe hypoproteinemia, low IgG concentration, and lymphopenia were suggestive of primary intestinal lymphangiectasia with protein-losing enteropathy, and the patient was placed on a low-fat diet with medium-chain triglycerides. This initially improved his condition, but some weeks later he developed obstructive ileus of the small intestine. On laparotomy yellowish to whitish deposits were found to be present in some segments of the small intestine and a fist-sized mass 100 cm distal to the duodenojejunal flexure was resected without complications. Histologically, the submucosal lymphatics were dilated, and the jejunal wall showed extensive pseudocystic, intramural submucosal lymph edema with secondary bleeding and tight stenosis of the jejunal lumen. During the 14-month follow-up time after discharge the patient has been asymptomatic and working, on no treatment other than a low-fat diet with medium-chain triglycerides.
5'-(N-ethylcarboxamido)-adenosine (NECA) and N-[(R)-(phenylisopropyl)]-adenosine (PIA) were incubated in an adenylate cyclase assay of a particulate fraction of caudate-putamen tissue of the rat in order to examine the effect of somatostatin on adenosine receptors coupled adenylate cyclase subunits in vitro. Somatostatin was able to inhibit the enhancement of cyclic AMP formation induced by NECA in the presence of the hydrolysable guanine nucleotide guanosine-triphosphate. The adenosine receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine as well as the somatostatin receptor antagonist cyclo (7-aminoheptanoyl-Phe-D-Trp-Lys-O-benzyl-Thr) did not influence somatostatin induced inhibition of NECA-activated adenylate cyclase. Somatostatin did not modulate the effect mediated by the A-1 adenosine receptor agonist PIA. Both pertussis toxin and cholera toxin activated striatal adenylate cyclase acting on the guanine nucleotide regulatory subunit of the enzyme. The stimulation induced by pertussis toxin was antagonized by somatostatin, while in presence of cholera toxin somatostatin enhanced cyclic AMP formation. These results suggest that somatostatin acts through a stimulatory as well as an inhibitory guanine nucleotide regulatory protein subtype to affect probably postsynaptic A-2 adenosine receptor coupled adenylate cyclase activity.
A two-stage study was carried out to characterize the bile and plasma lipid composition in normolipidemic non-obese patients with and without cholesterol gallstones. The first stage involved 11 patients with cholesterol gallstones admitted for elective cholecystectomy and a control group of 16 patients without cholesterol gallstones undergoing elective laparotomy. Bile samples were obtained intraoperatively by aspiration from the gallbladder. The bile of all the gallstone patients was supersaturated with cholesterol and its nucleation time was much shorter than that of bile in the control group (2.5 days vs 22.5 days, respectively, P < 0.001). The biliary fatty acid profile of phosphatidylcholine (PC) and free fatty acids (FFA) of gallstone patients was similar to that of the control group. C-22 fatty acids were found in a higher concentration in the FFA than in the PC fatty acids (P < 0.05) in both groups of patients. Plasma triglyceride levels in the gallstone patients were significantly higher than those in the control group and the biliary cholesterol level correlated with that of plasma triglycerides. In the second stage of the study, plasma lipid profiles were obtained in two additional groups of patients, 20 patients with and 24 patients without cholesterol gallstones, for an in-depth characterization of the differences in plasma lipid profiles. The gallstone patients were found to have not only significantly higher concentrations of plasma triglycerides but increased cholesterol and phospholipid level as well. These differences were essentially due to a higher lipid content of the plasma VLDL fraction, similar to the pattern of patients with type IV hyperlipoproteinemia.
Explore the source record for details and available documents.
A case with the combination of hypothyroidism and true myotonia is reported, in which the latter first became manifest clinically together with the thyroid disorder and improved with L-thyroxine therapy. The hypothyroidism itself caused very few symptoms, and the diagnosis was not made until examination for myotonia. The effect of each disorder on muscle function seems to be additive.
We have used a fluorescence-activated cytotoxicity protocol, 9-(1'-pyrene)nonanol (P9OH)/UV selection (Morand, O. H., Allen, L.-A. H., Zoeller, R. A., and Raetz, C. R. H. (1990) Biochim. Biophys. Acta 1034, 132-141), to isolate a series of plasmalogen-deficient mutants in a murine, macrophage-like cell line, RAW 264.7. Three of these mutants, RAW.7, RAW.12, and RAW.108, displayed varying degrees of plasmalogen deficiency (48, 17, and 14% of wild-type levels, respectively), and all three mutants were deficient in peroxisomal dihydroxyacetone phosphate (DHAP) acyltransferase activity (5% of wild-type). Unlike previously described Chinese hamster ovary (CHO) cell mutants, the RAW mutants contained intact, functional, peroxisomes and normal levels of alkyl-DHAP synthase activity, a peroxisomal, membrane-bound enzyme. In RAW.7 and RAW.108 cells, the loss of peroxisomal DHAP acyltransferase is the primary lesion. RAW.12 displayed not only a deficiency in the DHAP acyltransferase activity, but also displayed a second lesion in the biosynthetic pathway, a deficiency in delta 1'-desaturase activity (plasmanylethanolamine desaturase, EC 1.14.99.19), the final step in plasmenylethanolamine biosynthesis. The deficiencies expressed in the mutants represent unique lesions in plasmalogen biosynthesis. Since the RAW cell line is a macrophage-like responsive cell line, these mutants can be used to examine the role of plasmalogens in cellular functions such as arachidonic acid metabolism, prostaglandin synthesis, protein secretion, and signal transduction.
At least three slow myosin heavy chain (MHC) isoforms were expressed in skeletal muscles of the developing chicken hindlimb, and differential expression of these slow MHC isoforms produced distinct fiber types from the outset of skeletal muscle myogenesis. Immunohistochemistry with isoform-specific monoclonal antibodies demonstrated differences in MHC content among the fibers of the dorsal and ventral premuscle masses and distinctions among fibers before splitting of the premuscle masses into individual muscles (Hamburger and Hamilton Stage 25). Immunoblot analyses by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of myosin extracted from the hindlimb demonstrated the presence throughout development of different mobility classes of MHCs with epitopes associated with slow MHC isoforms. Immunopeptide mapping showed that one of the MHCs expressed in the embryonic limb was the same slow MHC isoform, slow MHC1 (SMHC1), that is expressed in adult slow muscles. SMHC1 was expressed in the dorsal and ventral premuscle masses, embryonic, fetal, and some neonatal and adult hindlimb muscles. In the embryo and fetus SMHC1 was expressed in future fast, as well as future slow muscles, whereas in the adult only the slow muscles retained expression of SMHC1. Those embryonic muscles destined in the adult to contain slow fibers or mixed fast/slow fibers not only expressed SMHC1, but also an additional slow MHC not previously described, designated as slow MHC3 (SMHC3). Slow MHC3 was shown by immunopeptide mapping to contain a slow MHC epitope (reactive with mAb S58) and to be structurally similar to a MHC expressed in the atria of the adult chicken heart. SMHC3 was designated as a slow MHC isoform because (i) it was expressed only in those muscles destined to be of the slow type in the adult, (ii) it was expressed only in primary fibers of muscles that subsequently are of the slow type, and (iii) it had an epitope demonstrated to be present on other slow, but not fast, isoforms of avian MHC. This study demonstrates that a difference in phenotype between fibers is established very early in the chicken embryo and is based on the fiber type-specific expression of three slow MHC isoforms.
The TIQ derivatives 2-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (2-MDTIQ) and 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (1-MDTIQ, salsolinol) were identified the first time as possible endogenous neurotoxins in parkinsonian but not in normal human lumbar cerebrospinal fluid by high performance liquid chromatography with electrochemical detection. Additionally, MDTIQ analogues were incubated with a monoamine oxidase (MAO) assay. MAO was able to metabolize dose-dependently 2-MDTIQ, whereas 1-MDTIQ was not modified by the enzyme.
Somatostatin, substance P, and vasoactive intestinal polypeptide were incubated in an adenylate cyclase assay with a particulate fraction of caudate-putamen tissue of the rat in order to examine the effect of the neuropeptides on G-protein coupled adenylate cyclase in vitro. Somatostatin induced an enhancement of cyclic AMP formation in presence of guanine nucleotides and cholera toxin but inhibited pertussis toxin and forskolin enzyme stimulation. Pertussis toxin and cholera toxin also depressed forskolin-induced stimulation as described previously. Somatostatin was able to antagonize these inhibitory effects of both toxins. On the contrary, substance P reduced GTP and cholera toxin stimulated striatal adenylate cyclase, without affecting forskolin activation. In our preparation, VIP did not influence basal adenylate cyclase activity or the stimulation by guanine nucleotides, cholera toxin, and pertussis toxin. VIP potently inhibited the enhancement of cyclic AMP formation by forskolin and completely antagonized the inhibitory effect of cholera toxin on forskolin activation. These results suggest that neuromodulatory effects of somatostatin, substance P, and VIP are mediated by the inhibitory as well as stimulatory guanine nucleotide proteins G-i and G-s coupled to an adenylate cyclase system.
The aim of this study was to determine the bidirectional release of immunoreactive inhibin-alpha (irINH-alpha) by different testicular compartments in the adult ram and to assess the effects of FSH on the distribution of inhibin in the testis. Immunoreactive INH-alpha was measured by RIA in fluid samples collected concurrently from the three testicular compartments--the seminiferous tubules, the interstitium, and the vascular system--through catheters inserted surgically into the rete testis, testicular lymphatic duct system, and spermatic veins, respectively. Overall, the concentration of irINH-alpha in rete testis fluid was 25 times the level in testicular lymph and over 500 times the concentration in peripheral blood. The pattern of irINH-alpha concentration in rete testis fluid was inversely related to that in testicular lymph, but i.v. administration of FSH had a decoupling effect on this relationship by depressing inhibin concentration in testicular lymph without affecting inhibin levels in rete testis fluid. Nevertheless, increased flow of testicular lymph more than compensated for the transient fall in irINH-alpha concentration so that, overall, the total output of inhibin via the testicular lymphatic duct system (and the vascular system) increased significantly. No persistent or significant changes were observed in the flow rate of rete testis fluid or concentration of irINH-alpha in the fluid after administration of FSH. The time frame for the response of the testis to FSH is indicative of the involvement of a mediator. Electrophoretic analysis of serially collected testicular lymph samples consistently revealed an FSH-induced release of a series of proteins in the M(r) range of 30,000-32,000.(ABSTRACT TRUNCATED AT 250 WORDS)
5'-(N-Ethylcarboxamido)adenosine (NECA) and N6-[(R)-(phenylisopropyl)]adenosine (PIA) were incubated in an adenylate cyclase assay with a particulate fraction of caudate-putamen tissue of the rat, in order to examine the effect of kainic acid and a 6-hydroxydopamine-induced lesion on adenosine receptor coupled adenylate cyclase in vitro. There was an enhancement of formation of cyclic AMP induced by NECA, that was mediated by A2 adenosine receptors. Phenylisopropyl adenosine also stimulated adenylate cyclase in the striatum, with a maximum increase at 0.1 mM. At smaller concentrations, PIA inhibited the basal activity, which was previously described to be an effect mediated by A1 adenosine receptors. In caudate-putamen tissue from rats receiving a unilateral lesion, induced with kainic acid, basal and maximally NECA- and PIA-stimulated activity of adenylate cyclase was decreased. The maximum stimulatory effects of both substances were also significantly decreased, whereas no change of the inhibitory effect of PIA was observed. After unilateral lesion induced with 6-OHDA, basal and maximally NECA- and PIA-activated adenylate cyclase was increased; however, no inhibitory effect of PIA was seen. These results suggest that A2 adenosine receptor-coupled adenylate cyclase was located on neurones intrinsic to the neostriatum and probably postsynaptic to the dopaminergic input. The A1 adenosine receptors seem to be associated with the nigrostriatal pathway implying a presynaptic localization on dopaminergic afferents. In addition, since after both kainic acid- and 6-OHDA-induced lesions, respectively, in caudate-putamen tissue of the contralateral side, PIA no longer inhibited the activity of adenylate cyclase, contralateral structures also appeared to be involved in the regulation of A1 adenosine receptors.
Explore the source record for details and available documents.
The B isoform of creatine kinase (BCK), which is expressed at a high level in embryonic neural tissues, is also expressed abundantly in developing striated muscle and is an early marker for skeletal myogenesis. Using isoform-specific 35S-labeled antisense cRNA probes for in situ hybridization, we have detected BCK mRNAs in embryonic mouse and chick myotomes, the first skeletal muscle masses to form in developing embryos. These transcripts are detectable as soon as myotomes are morphologically distinguishable. BCK is expressed at high levels in both skeletal and cardiac muscle in mouse and chick embryos. In the mouse, BCK transcript levels fall of rapidly in striated muscle shortly after the onset of MCK gene expression. The M isoform of creatine kinase (MCK), the striated muscle-specific isoform, is expressed later than BCK. In the mouse, BCK transcripts are expressed in myotomes at 8.5 days post coitum (p.c.), but MCK transcripts are not detected before 13 days p.c. In the chick, BCK mRNAs are present at Hamburger-Hamilton stage 13, but MCK mRNAs are not detected before stage 19. We have compared the patterns of expression of the CK genes with those of myogenic differentiation factor genes, which are thought to regulate skeletal muscle-specific gene expression. In the chick, both CMD1, first detected at stage 13, and myogenin, first detected at stage 15, are present prior to MCK, which begins to be expressed at stage 19. Unlike the mouse embryo, CMD1, the chick homologue of MyoD1, is expressed before chick myogenin. In the mouse, myogenin, first detected at 8.5 days p.c., is expressed at the same time as BCK in myotomes. Both myogenin and MyoD1, which begins to be detected two days later than myogenin, are expressed at least two days before MCK. It has been proposed that the myogenic factors, MyoD1 and myogenin, directly regulate MCK gene expression in the mouse by binding to its enhancer. However, our results show that MCK transcripts are not detected until well after MyoD1 and myogenin mRNAs are expressed, suggesting that these factors by themselves are not sufficient to initiate MCK gene expression.
The effects of iron ions (Fe(II)sulfate) on basal, forskolin, and dopamine-stimulated activity of adenylate cyclase in membrane preparations from caudate-putamen of the rat have been studied. Iron dose-dependently inhibited both basal and activated adenylate cyclase activity. In contrast to guanylylimidodiphosphate (Gpp(NH)p), guanosine triphosphate (GTP) was found to enhance this inhibitory effect of iron ions. In addition, cholera toxin was able to antagonize the inhibitory effect of iron on forskolin-activated adenylate cyclase. In our preliminary study we suggest an interaction between iron and the guanine nucleotide regulatory subunit. However, further studies are necessary.