Diffuse unilateral subacute neuroretinitis syndrome in a German most likely caused by the raccoon roundworm, Baylisascaris procyonis.
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Acute Disease↗
Biomedical subjects
C Bauer
Publications and source records attributed to C Bauer.
Lack of associations between fetal and maternal serum-erythropoietin at birth.
Erythropoietin (EPO) is known to be the main regulator of erythropoiesis. We wanted to determine whether EPO production during pregnancy takes place independently in the mother and the fetus, and to identify the factors which set the EPO level. Endogenous EPO levels were determined in simultaneous samples from the umbilical vein, the umbilical artery and a maternal vein in 126 mother-child pairs and simultaneously from amniotic fluid (n = 14) in unselected births. Results were related to clinical and biochemical parameters of fetal well-being, mode of delivery, duration of labor, and infant parameters at birth. There was a weak correlation between maternal and fetal log EPO values (umbilical vein: r2 = 0.11; umbilical artery: r2 = 0.08), but a highly significant correlation between log EPO levels in the two umbilical vessels (r2 = 0.91) and between both umbilical blood and amniotic fluid (r2 = 0.41). Maternal EPO levels were lower than fetal levels in 76 cases, higher in 47, and nearly identical in 3. Increased fetal EPO levels were associated with clinical and biochemical indicators of fetal stress. These associations help to explain why EPO concentrations in fetal blood are independent of maternal levels and also indicate that EPO does not cross the placental barrier. These findings are discussed in the light of the animal experimental and in vitro evidence for placental transfer of EPO. Our data, and the work of others, make such a transfer in humans quite unlikely. This observation has therapeutical consequences for the treatment of maternal anemia with recombinant human EPO.
Amniotic Fluid↗
Control of photosystem genes in Rhodobacter capsulatus.
Two environmental factors, oxygen and high light intensity, are known to repress synthesis of the Rhodobacter capsulatus photosystem. One level of regulation is the control of light harvesting and reaction centre gene expression at the point of transcription initiation. This has recently been shown to involve transcriptional activators which exhibit sequence similarity to members of the 'two-component' class of prokaryotic regulators. An additional level of regulation involves the formation of 'superoperons' that transcriptionally link pigment biosynthesis operons with operons that code for the light harvesting and reaction centre structural genes. A final level of regulation involves the selective degradation of reaction centre mRNA transcripts which influence the stoichiometric synthesis of the light harvesting and reaction centre complexes.
Anaerobiosis↗
In-vivo assessment of DNA ligation efficiency and fidelity in cells from patients with Fanconi's anemia and other cancer-prone hereditary disorders.
We developed a host cell DNA ligation assay, in which we transfected linearized plasmid pZ189 into human lymphoblasts or fibroblasts in order to assess the efficiency and accuracy of DNA ligation within these host cells. We used cell lines from patients with Fanconi's anemia and other chromosome breakage or instability syndromes (Bloom's syndrome, ataxia telangiectasia, Werner's syndrome). With the Fanconi's anemia lymphoblast line GM8010 we did not find a reduced, but a slightly hypermutable DNA ligation. Mutation analysis revealed a unique 7.9-12.5-fold increase in insertions or complex mutations. With cells from the other chromosome breakage/instability syndromes we also found a hypermutable and/or reduced DNA ligation. An impaired DNA ligation might be a common molecular mechanism of genetic instability in these disorders.
Cell Line↗
The role of receptor binding in drug discovery.
Radioligand receptor binding has been used extensively to identify and characterize a host of receptors and enzymes targeting virtually every therapeutic area. Many drug discovery programs have been based on the utilization of radioligand receptor binding technology to identify lead compounds which interact with receptors likely to be important in neuronal, immunological, gastrointestinal, and cardiovascular function/dysfunction. There are several obvious advantages to using in vitro receptor binding as a first level screen when compared to in vivo pharmacometric screens. Scientifically, the structure activity data generated in binding assays is a direct reflection of the ligand/receptor interaction minus the complications which result from secondary events, bioavailability, and pharmacodynamic issues. Technically, the binding studies require only a small amount of test compound (< or = 1 mg), while whole animal studies routinely need gram quantities. Similarly, only a small amount of tissue is required, compared with the cost of purchase and maintenance of live animals for in vivo screening. Supply and labor costs are drastically reduced due to the limited volume and test tube based technology of receptor binding. For these reasons receptor binding assays have been utilized with considerable success to discover site specific lead compounds in virtually every therapeutic area.
Animals↗
Influence of dopaminergic agonists/antagonists on fucose metabolism in the rat brain.
UNLABELLED: Valid indications of a key role for dopaminergic drugs in glycoprotein fucosylation in neuronal tissue in vitro led us to investigate whether the administration of dopaminergic agonists/antagonists influences fucose metabolism in the rat brain in vivo. Three test groups were set up. Group 1 was given L-DOPA (210 mg/l), Group 2 haloperidol (10.5 mg/l) in drinking water, Group 3 served as control. The rats were sacrificed after 8 weeks and enzyme activities in 5 different brain areas were determined concerning the enzymes of the anabolic fucose metabolism: fucokinase, fucose-1-phosphate pyrophosphorylase and fucosyltransferase 1 and 2. Only the specific activity of fucokinase was affected by haloperidol or L-DOPA administration. In the olfactory bulbus, thalamus and cortex, haloperidol decreased fucokinase activity by 21%, 37%, and 39%, respectively (p < 0.05 in each case). No changes were observed in the cerebellum and striatum. Surprisingly, fucokinase activity in the cortex was decreased by L-DOPA (31%, p < 0.05). CONCLUSIONS: Cerebral fucokinase activity is influenced in vivo by dopaminergic drugs in well circumscribed brain areas. Other enzymes of the anabolic fucose metabolism showed no change in activity. It is, therefore, conceivable that these drugs, apart from known mechanisms, exert part of their pharmacological action via a modulation of fucose metabolism.
Animals↗
Leukocyte-endothelial cell interactions in the liver after hemorrhagic shock in the rat.
Leukocyte-endothelial cell interactions in rat livers were investigated using intravital fluorescence microscopy following hemorrhagic shock (MAP at 40 mm Hg for 60 min) and resuscitation. Thirty minutes after resuscitation, when MAP was higher than 100 mm Hg, sinusoidal perfusion was only slightly reduced (>90% of controls). Firm adhesion of leukocytes increased to 370 +/- 54 leukocytes/mm2 after shock and resuscitation compared to control animals (48 +/- 8/mm2; mean +/- SEM; P < .01). Leukocyte-endothelium adhesion was highest in the portal areas and lowest in midzonal and pericentral regions (relationship:2.0: 1.1:1.0). Pretreatment with dexamethasone (5 mg/kg bw) resulted in a dramatic rise of adherent leukocytes following hemorrhagic shock (920 +/- 62/mm2; P < .001). Pretreatment with ibuprofen (15 mg/kg bw) resulted in a similar increase of adherent leukocytes after hemorrhagic shock (750 +/- 60/mm2; P < .001), while pretreatment with MK 886(10 mg/kg), inhibitor of lipoxygenase pathway, reduced leukocyte adhesion slightly (270 +/- 38/mm2). The results reveal that leukotrienes, e.g., released by activated macrophages, are involved in the regulation of leukocyte adhesion in liver sinusoids following hemorrhagic shock and resuscitation. The negative effect of dexamethasone and ibuprofen on hepatic leukocyte adhesion, however, has to be considered for therapeutic use.
Animals↗
Inhibitory effect of zinc on stimulated erythropoietin synthesis in HepG2 cells.
The effect of zinc on erythropoietin (EPO) synthesis in HepG2 cells was investigated. The increase in EPO synthesis induced by Co2+ (50 microM), Ni2+ (300 microM) or oxygen (1% O2) was inhibited by the presence of ZnCl2 (50-150 microM) in the tissue-culture medium, whereas basal EPO synthesis was unaffected. The effect was reflected by corresponding changes in the EPO mRNA level. These effects of zinc on EPO synthesis could not be mimicked by CdCl2 (less than or equal to 2 microM). Addition of FeCl3 to the medium appeared to decrease the inhibitory effect of zinc on hypoxia-induced EPO synthesis, implying that zinc may interfere with an iron-dependent step in EPO regulation.
Blotting, Northern↗
Intracellular distribution of endothelin-1 receptors in rat liver cells.
We studied the binding of (125I)-endothelin-1 as well as that of the vasopressin analogue (125I)-[8-phenylpropionyl]-LVP to purified plasma membranes, Golgi cisternae and cell nuclei from rat liver. Cell organelles were isolated by differential centrifugation and discontinuous sucrose gradients. Endothelin-1 exhibited specific binding to plasma membranes, Golgi cisternae and nuclei, while the binding of (125I)-[8-phenylpropionyl]-LVP was restricted to the plasma membranes. The number of receptors (Bmax) and the binding constants (Kd) were determined by Scatchard analysis of competition binding studies. In all cases only one class of Et-1 binding sites could be detected. The presence of Et-1 receptors on the Golgi complex either indicates that the receptor is glycosylated within the cisternae or alternatively, there exists a recycling pathway. The unexpected finding of Et-1 receptors on highly purified nuclei suggests that this peptide may exert part of its biological functions intracellularly via the nucleus.
Animals↗
Inhibition of N-acetylglucosamine kinase and N-acetylmannosamine kinase by 3-O-methyl-N-acetyl-D-glucosamine in vitro.
During the search for inhibitors of N-acetylneuraminic acid biosynthesis, it was shown that 3-O-methyl-N-acetylglucosamine competitively inhibits the N-acetylglucosamine kinase of rat liver in vitro with a Ki value of 17 microM. N-Acetylmannosamine kinase is inhibited non-competitively with a Ki value of 80 microM. In a human hepatoma cell line (HepG2), 3-O-methyl-N-acetyl-D-glucosamine (1 mM) inhibits the incorporation of 14C-N-acetylglucosamine and 14C-N-acetylmannosamine into cellular glycoproteins by 88% and 70%, respectively.
Acetylglucosamine↗
Inhibition of the biosynthesis of N-acetylneuraminic acid by metal ions and selenium in vitro.
In liver homogenate the biosynthesis of N-acetylneuraminic acid using N-acetylglucosamine as precursor can be followed stepwise by applying different chromatographic procedures. In this cell-free system 16 metal ions (Zn2+, Mn2+, La3+, Co2+, Cu2+, Hg2+, VO3-, Pb2+, Ce3+, Cd2+, Fe2+, Fe3+, Al3+, Sn2+, Cs+ and Li+) and the selenium compounds, selenium(IV) oxide and sodium selenite, have been checked with respect to their ability to influence a single or possibly several steps of the biosynthesis of N-acetylneuraminic acid. It could be shown that the following enzymes are sensitive to these metal ions (usually applied at a concentration of 1 mmol l-1): N-acetylglucosamine kinase (inhibited by Zn2+ and vandate), UDP-N-acetylglucosamine-2'-epimerase (inhibited by Zn2+, Co2+, Cu2+, Hg2+, VO3-, Pb2+, Cd2+, Fe3+, Cs+, Li+, selenium(IV) oxide and selenite), and N-acetylmannosamine kinase (inhibited by Zn2+, Cu2+, Cd2+ and Co2+). Dose dependent measurements have shown that Zn2+, Cu2+ and selenite are more efficient inhibitors of UDP-N-acetylglucosamine-2'-epimerase than vanadate. As for the N-acetylmannosamine kinase inhibition, a decreasing inhibitory effect exists in the following order Zn2+, Cd2+, Co2+ and Cu2+. In contrast, La3+, Al3+ and Mn2+ (1 mmol l-1) did not interfere with the biosynthesis of N-acetylneuraminic acid. Thus, the conclusion that the inhibitory effect of the metal ions investigated cannot be regarded as simply unspecific is justified.
Acetylglucosamine↗
On the nature of non-genotoxic carcinogens. A unified theory including NGCs, co-carcinogens and promoters.
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Animals↗
World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) methods for the detection of anthelmintic resistance in nematodes of veterinary importance.
Methods have been described to assist in the detection of anthelmintic resistance in strongylid nematodes of ruminants, horses and pigs. Two tests are recommended, an in vivo test, the faecal egg count reduction test for use in infected animals, and an in vitro test, the egg hatch test for detection of benzimidazole resistance in nematodes that hatch shortly after embryonation. Anaerobic storage for submission of faecal samples from the field for use in the in vitro test is of value and the procedure is described. The tests should enable comparable data to be obtained in surveys in all parts of the world.
Animals↗
Isolation of plasma membranes from keratinocytes: a newly developed method allows the sensitive detection of the membrane antigen pattern in normal and psoriatic skin.
Distinct differences of proteins in the plasma membranes have been described in psoriatic keratinocytes as compared with normal epidermis. These changes are presumably involved in the pathogenesis of psoriasis. To identify and distinguish glycosylated proteins of the plasma membranes of keratinocytes, a method for mild preparation was developed that avoids the use of degrading or digestive enzymes. After cell lysis, three steps of centrifugation were performed, including the use of a sucrose step gradient. A fine-vesicular membrane fraction was obtained. Using marker enzymes for cell compartments, no contamination of cell nuclei or mitochondria and only 0.4% of endoplasmic reticulum was detectable in the final membrane fraction. Based on this preparation, disc-polyacrylamide-gel electrophoresis, followed by Western blotting, were performed. Staining with five different lectins to visualize glycosylated proteins allowed 75 different membrane glycoproteins to be distinguished. The patterns of normal, transformed (HaCaT), foreskin and psoriatic keratinocytes after cell culture with one passage were compared. Up to six proteins per lectin staining were expressed differently in psoriatic as compared to normal keratinocytes. Psoriatic cells shared similarities with highly proliferative foreskin cells, but not with transformed HaCaT cells. Main alterations of glycosylation were detected in the fucose content. In conclusion, the method developed for isolation of plasma membranes allows selective and sensitive examination of plasma membranes of normal and pathological keratinocytes. The glycosylation patterns observed suggest that distinct membrane proteins may be involved in the pathogenesis of psoriasis.
Antigens, Surface↗
Insulin-like growth factors decrease oxygen-regulated erythropoietin production by human hepatoma cells (Hep G2).
We examined the effects of insulin-like growth factors (IGFs) and insulin on erythropoietin (EPO) production by human hepatoma cells (Hep G2). Compared with normoxia (20% O2), EPO production by Hep G2 cells during a 72-h incubation was stimulated fivefold by exposure to low oxygen tension (1% O2) and nearly threefold by exposure to cobalt chloride (100 microM). IGF-I caused a concentration-dependent attenuation of EPO formation under normoxic conditions and inhibited (maximally 50%) EPO production stimulated by either low oxygen tension or cobalt [half-maximal effect (ED50) approximately 5 nM]. The increase of EPO mRNA levels in response to hypoxia was significantly reduced by IGF-I. Similarly to IGF-I, IGF-II (ED50 approximately 8 nM) and insulin (ED50 approximately 80 nM) also inhibited EPO formation in Hep G2 cells. IGF-I (100 pM-100 nM) stimulated the incorporation of radiolabeled alanine as a measure for total protein synthesis, 3H-labeled thymidine incorporation into DNA, and glycogen synthesis at 20 and 1% O2 in a concentration-dependent fashion. IGF-I exhibited a high affinity for the IGF-I receptor (apparent Kd approximately 3 nM). Unlabeled insulin was greater than 100-fold less potent than IGF-I in competing for 125I-IGF-I binding (apparent Kd approximately 360 nM). Conversely, insulin bound to the insulin receptor with high affinity (apparent Kd approximately 0.3 nM), whereas IGF-I was less than 1% as potent in competing for 125I-insulin binding. In summary, IGFs and insulin exert a negative control function on oxygen-regulated EPO production in Hep G2 cells. The inhibitory effect of IGFs and insulin on EPO formation appears to be mediated via the IGF-I receptor.
Animals↗
Age-dependent expression of the erythropoietin gene in rat liver and kidneys.
Using RNAse protection, we have made quantitative measurements of erythropoietin (EPO) mRNA in liver and kidneys of developing rats (days 1-54), to determine the relative contribution of both organs to the total EPO mRNA, to monitor changes which occur with development, and to compare the hypoxia-induced accumulation of EPO mRNA with the changes in serum EPO concentrations. To determine whether developmental and organ-specific responsiveness is related to the type of hypoxic stimulus, normobaric hypoxia was compared with exposure to carbon monoxide (functional anemia). Under both stimuli EPO mRNA concentration in liver was maximal on day 7 and declined during development. In contrast, EPO mRNA concentration in kidney increased during development from day 1 when it was 30-65% the hepatic concentration to day 54 when it was 12-fold higher than in liver. When organ weight was considered the liver was found to contain the majority of EPO mRNA in the first three to four weeks of life, and although, in stimulated animals, the hepatic proportion declined from 85-91% on day 1, it remained approximately 33% at day 54 and was similar for the two types of stimuli. When normalized for body weight the sum of renal and hepatic EPO mRNA in animals of a particular age was related linearly to serum hormone concentrations. However, the slope of this regression increased progressively with development, suggesting age-dependent alterations in translational efficiency or EPO metabolism.
Age Factors↗
[Use of anthelmintics for nematode control in sheep in West Germany: results of a survey].
A survey by questionnaires was performed on 543 (0.9% of all) sheep flocks in western Germany in 1988/89 to obtain informations about deworming practices against gastrointestinal nematodes. The major informations are: Anthelmintic treatments were associated with the reproductive status of ewes and the breeding of lambs in most of the flocks. They were performed at an epidemiologically appropriate time in many cases but were not accompanied by essential management practices. (Pro)benzimidazole compounds were the anthelmintics most frequently used by more than 95% of the farmers; 22% and 13% of the farmers additionally or exclusively administered levamisole/pyrantel and ivermectin, respectively. On average, treatment of ewes and lambs against nematodes was performed 2.5 times and 2.8 times a year, respectively. The mean frequency of deworming differed regionally and was generally greater in pedigree breeding flocks than in commercial breeding flocks; it was significantly affected by the husbandry system, the number of ewes per flock, the size of available pasture and the class of anthelmintics employed. The results of this survey revealed that many German sheep farmers obviously lack an awareness of the rationale of preventive and economic control practices against gastrointestinal nematodes.
Animals↗
HIV-1 seroprevalence in pregnant women testing positive on serologic screening for syphilis.
Epidemic increases in active syphilis have been reported in the geographic areas hit hard by acquired immunodeficiency syndrome. Although both epidemics have been associated with illicit substance abuse, the extent to which recent increases in syphilis are linked to the human immunodeficiency virus (HIV-1) epidemic is uncertain. In order to define the frequency of syphilis and HIV-1 coinfection in the pregnant patients seen at City Hospital Center at Elmhurst, we saved syphilis-positive serologic specimens from obstetrical patients for anonymous HIV-1 antibody testing. Of 120 women who tested positive for syphilis, 7/120 (5.8%) had antibodies to HIV-1; of the 44 women with VDRL titers greater than or equal to 1:16 (suggestive of a recent infection), 1/44 (2.3%) had antibodies to HIV-1.
Female↗