[Thirty-year old woman with severe iron deficiency anemia and weight loss of unknown etiology].
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Adenocarcinoma↗
Biomedical subjects
C Lang
Publications and source records attributed to C Lang.
Perspectives in the biological function and the technological application of polygalacturonases.
Polygalacturonases (PG) have evolved in the past years from a pectinase "simply" being used for food processing to an important parameter in plant-fungal interaction. PG-inhibiting proteins (PGIP) that are synthesised in plants as a specific response to PGs of pathogenic fungi, have become a focus as a possible target in resistance breeding, and PGIPs are also a concern as an inhibiting factor in food processing. Plant PGs have been identified as a major factor in fruit ripening, and PG-deficient transgenic plants have been bred. Mainly fungal PGs are used in industrial processes for juice clarification and the range of enzymes is being extended through new recombinant and non-recombinant fungal strains. Finally, novel fields of application can be envisaged for PGs in the production of oligogalacturonides as functional food components. Here we aim to highlight the various fields where PGs are encountered and where they are of biological or technological importance.
Food Technology↗
16 degrees C rapid temperature variation in central greenland 70,000 years Ago
Variations in the (29)N(2)/(28)N(2) ratio of air bubbles trapped in polar ice cores and their relation to variations of the (18)O/(16)O of the ice allow past surface temperature variations and ice age-gas age differences to be determined. High-resolution measurements of (29)N(2)/(28)N(2) in Dansgaard-Oeschger event 19 (around 70,000 years before the present) in ice from Central Greenland show that at the beginning of the event, the ice age-gas age difference was 1090 +/- 100 years. With the use of a combined firn densification, temperature, and gas diffusion model, the delta(18)O(ice)-temperature coefficient alpha was determined to be 0. 42 +/- 0.05 per mil per kelvin. This coefficient implies a mean surface temperature change of 16.0 kelvin (between 14.3 and 18.1 kelvin), which differs substantially from values derived from borehole temperatures and modern spatial delta(18)O(ice)-surface temperature correlations.
Journal Article↗
Daily sunscreen application and betacarotene supplementation in prevention of basal-cell and squamous-cell carcinomas of the skin: a randomised controlled trial.
BACKGROUND: The use of sunscreens on the skin can prevent sunburn but whether long-term use can prevent skin cancer is not known. Also, there is evidence that oral betacarotene supplementation lowers skin-cancer rates in animals, but there is limited evidence of its effect in human beings. METHODS: In a community-based randomised trial with a 2 by 2 factorial design, individuals were assigned to four treatment groups: daily application of a sun protection factor 15-plus sunscreen to the head, neck, arms, and hands, and betacarotene supplementation (30 mg per day); sunscreen plus placebo tablets; betacarotene only; or placebo only. Participants were 1621 residents of Nambour in southeast Queensland, Australia. The endpoints after 4.5 years of follow-up were the incidence of basal-cell and squamous-cell carcinomas both in terms of people treated for newly diagnosed disease and in terms of the numbers of tumours that occurred. Analysis of the effect of sunscreen was based only on skin cancers that developed on sites of daily application. All analyses were by intention to treat. FINDINGS: 1383 participants underwent full skin examination by a dermatologist in the follow-up period. 250 of them developed 758 new skin cancers during the follow-up period. There were no significant differences in the incidence of first new skin cancers between groups randomly assigned daily sunscreen and no daily sunscreen (basal-cell carcinoma 2588 vs 2509 per 100,000; rate ratio 1.03 [95% CI 0.73-1.46]; squamous-cell carcinoma 876 vs 996 per 100,000; rate ratio 0.88 [0.50-1.56]). Similarly, there was no significant difference between the betacarotene and placebo groups in incidence of either cancer (basal-cell carcinoma 3954 vs 3806 per 100,000; 1.04 [0.73-1.27]; squamous-cell carcinoma 1508 vs 1146 per 100,000; 1.35 [0.84-2.19]). In terms of the number of tumours, there was no effect on incidence of basal-cell carcinoma by sunscreen use or by betacarotene but the incidence of squamous-cell carcinoma was significantly lower in the sunscreen group than in the no daily sunscreen group (1115 vs 1832 per 100,000; 0.61 [0.46-0.81]). INTERPRETATION: There was no harmful effect of daily use of sunscreen in this medium-term study. Cutaneous squamous-cell carcinoma, but not basal-cell carcinoma seems to be amenable to prevention through the routine use of sunscreen by adults for 4.5 years. There was no beneficial or harmful effect on the rates of either type of skin cancer, as a result of betacarotene supplementation.
Adult↗
Enhanced sterol-acyl transferase activity promotes sterol accumulation in Saccharomyces cerevisiae.
The sterol-acyl transferase encoded by the gene ARE2 was transcriptionally deregulated in the yeast Saccharomyces cerevisiae to understand its role in sterol storage and sterol enrichment. Our results show that sterols can indeed be enriched in yeast by enhancing the capacity of the cells to esterify sterols. ARE2 overexpression had no impact on the accumulation of the early sterols such as lanosterol, but influenced the later intermediates and the end product ergosterol. Thus an enhanced conversion of free sterols to their esterified counterparts may provide a tool to increase the overall sterol content of the yeast cell. We have previously shown that the overexpression of a truncated version of the key enzyme of the early sterol pathway, HMG-CoA reductase (HMG1), leads to an increase in the early sterols such as lanosterol and zymosterol. The simultaneous deregulation of both genes in one strain produces a cumulative effect in that both early and late sterols are enhanced. Karmellae-like structures can be detected when Are2p is overexpressed. Are2p therefore constitutes a new member of the karmellae-inducing protein family.
Acyltransferases↗
A quantitative immunohistochemical study on the time-dependent course of acute inflammatory cellular response to human brain injury.
The time-dependent inflammatory cell reaction in human cortical contusions has been investigated during the first 30 weeks after blunt head injury. Immunohistochemical staining was carried out using CD 15 for granulocytes and LCA, CD 3 and UCHL-1 for mononuclear leucocytes. In order to provide reliable data for a forensic wound age estimation, the intensity of the cellular reaction was evaluated with a quantitative image analysis system. CD 15-labelled granulocytes were detectable earliest 10 min after brain injury, whereas significantly increased numbers of mononuclear leucocytes occurred in cortical contusions after a postinfliction interval of at least 1.1 days (LCA), 2 days (CD 3) or 3.7 days (UCHL-1), respectively.
Adolescent↗
Interspecies complementation in Saccharopolyspora erythraea : elucidation of the function of oleP1, oleG1 and oleG2 from the oleandomycin biosynthetic gene cluster of Streptomyces antibioticus and generation of new erythromycin derivatives.
Two glycosyltransferase genes, oleG1 and oleG2, and a putative isomerase gene, oleP1, have previously been identified in the oleandomycin biosynthetic gene cluster of Streptomyces antibioticus. In order to identify which of these two glycosyltransferases encodes the desosaminyltransferase and which the oleandrosyltransferase, interspecies complementation has been carried out, using two mutant strains of Saccharopolyspora erythraea, one strain carrying an internal deletion in the eryCIII (desosaminyltransferase) gene and the other an internal deletion in the eryBV (mycarosyltransferase) gene. Expression of the oleG1 gene in the eryCIII deletion mutant restored the production of erythromycin A (although at a low level), demonstrating that oleG1 encodes the desosaminyltransferase required for the biosynthesis of oleandomycin and indicating that, as in erythromycin biosynthesis, the neutral sugar is transferred before the aminosugar onto the macrocyclic ring. Significantly, when an intact oleG2 gene (presumed to encode the oleandrosyltransferase) was expressed in the eryBV deletion mutant, antibiotic activity was also restored and, in addition to erythromycin A, new bioactive compounds were produced with a good yield. The neutral sugar residue present in these compounds was identified as L-rhamnose attached at position C-3 of an erythronolide B or a 6-deoxyerythronolide B lactone ring, thus indicating a relaxed specificity of the oleandrosyltransferase, OleG2, for both the activated sugar and the macrolactone substrate. The oleP1 gene located immediately upstream of oleG1 was likewise introduced into an eryCII deletion mutant of Sac. erythraea, and production of erythromycin A was again restored, demonstrating that the function of OleP1 is identical to that of EryCII in the biosynthesis of dTDP-D-desosamine, which we have previously proposed to be a dTDP-4-keto-6-deoxy-D-glucose 3, 4-isomerase.
Chromatography, High Pressure Liquid↗
Rapid transbilayer movement of fluorescent phospholipid analogues in the plasma membrane of endocytosis-deficient yeast cells does not require the Drs2 protein.
Evidence is presented that endocytosis-deficient Saccharomyces cerevisiae end4 yeast cells rapidly internalize the fluorescent phospholipid analogues 1-palmitoyl-2-{6-[7-nitro-2,1, 3-benzoxadiazol-4-yl(NBD)amino] caproyl}phosphatidylcholine (P-C6-NBD-PtdCho) and P-C6-NBD-phosphatidylserine (P-C6-NBD-PtdSer). Both analogues redistributed between the exoplasmic and cytoplasmic leaflet with a half-time of < 15 min at 0 degrees C. The plateau of internalized analogues was about 70%. Transbilayer movement is probably protein-mediated, as the flip-flop of both analogues was very slow in liposomes composed of plasma-membrane lipids. Rapid analogue internalization was not abolished on depletion of intracellular ATP by about 90%. For P-C6-NBD-PtdCho only was a moderate decrease in the plateau of internalized analogues of about 20% observed, while that of P-C6-NBD-PtdSer was not affected. The Drs2 protein plays only a minor role, if any, in the rapid transbilayer movement of analogues in S. cerevisiae end4 cells. In S. cerevisiae end4 Deltadrs2 cells harbouring both an end4 allele and a drs2 null allele, about 60% and 50% of P-C6-NBD-PtdCho and P-C6-NBD-PtdSer, respectively, became internalized within 15 min at 0 degrees C. The preferential orientation of P-C6-NBD-PtdSer to the cytoplasmic leaflet is in qualitative agreement with the sequestering of endogenous phosphatidylserine to the cytoplasmic leaflet, as assessed by binding of annexin V. Virtually no binding of annexin V to spheroplasts of the parent wild-type strain or the mutant strains was observed. Likewise, no difference in the exposure of endogenous aminophospholipids to the exoplasmic leaflet between these strains was found by labelling with trinitrobenzenesulfonic acid. Thus, lipid asymmetry, at least of aminophospholipids, was preserved in S. cerevisiae end4 cells independently of the presence of the Drs2 protein.
4-Chloro-7-nitrobenzofurazan↗
[Sports injuries of the nervous system].
Almost 1% of all Germans suffer sports injuries each year, almost 5% of all peripheral nerve lesions are due to sports. A review is given on various activities detailing the specific risks for traumata of the central and peripheral nervous system. Specifically these are volleyball, handball, basketball, American football, soccer, bowling, hockey, baseball, tennis, golf, javelin, fencing, wrestling, judo, boxing, running, jumping, dancing, mountain climbing, weight lifting, gymnastics, horse-back riding, swimming, rowing, skiing, skating, shooting, (motor) biking, car racing, flying, and sports for the disabled. The knowledge of typical traumata should enable the neurologist to rapidly and reliably recognize related lesions and to contribute to their prevention or improvement.
Athletic Injuries↗
High rates of appendicectomy in a developing country: an attempt to contribute to a more rational use of surgical resources.
OBJECTIVE: In view of the high appendicectomy rate in a university teaching hospital in a developing country, we investigated the regional epidemiology of appendicitis. DESIGN: Prospective clinical and pathological study. SETTING: Teaching hospital, Madagascar. SUBJECTS: 165 patients who underwent appendicectomy during a two month period. INTERVENTIONS: Clinical investigation and histopathological examination of removed appendixes. MAIN OUTCOME MEASURES: Appendicitis score, local incidence of appendicectomy, appendicitis, perforation, and negative appendicectomy. RESULTS: There was a high incidence of primary appendicectomy (51.1/10,000 population/year) in relation to the incidence of histologically confirmed appendicitis (7.7/10,000), resulting in a negative appendicectomy rate of 85% (43/10,000). There were considerable sex related differences in the incidence of primary appendicectomy (81/10,000 women/year; 22/10,000 men), appendicectomy for appendicitis (12/10,000 women/year; 4/10,000 men) and non-perforating appendicitis (8/10,000 women/year; 2/10,000 men), but much less in that of perforating appendicitis (4/10,000 women/year; 2/10,000 men). CONCLUSION: There is potential for more economic use of medical resources by reducing the rate of negative appendicectomy. The incidence of non-perforating appendicitis depends on the number of appendicectomies done, which may explain the differences observed in the incidence of appendicitis between industrialised and developing countries.
Appendectomy↗
Propofol-thiopentone admixture-hypnotic dose, pain on injection and effect on blood pressure.
This study examined some pharmacodynamic characteristics of two admixtures of propofol and thiopentone. Ninety unpremedicated ASA 1 or 2 patients were group-randomized to receive, in a double-blinded manner, one of the following mixtures for induction of anaesthesia: Group P50: propofol 1% 10 ml/thiopentone 2.5% 10 ml; Group P75: propofol 1% 15 ml/thiopentone 2.5% 5 ml; Group P100: propofol 1% 20 ml/lignocaine 1% 4 ml. An additional 30 randomized but unblinded patients from the same patient cohort received thiopentone 2.5% to provide predictive dose data for groups P50 and P75. Haemodynamic data were collected pre- and post-induction. The required induction dose of both mixtures of propofol and thiopentone found an additive rather than a synergistic interaction with no significant difference between predicted and observed dose. Thiopentone resulted in significantly more rapid induction of anaesthesia than propofol/lignocaine or propofol/thiopentone. The addition of thiopentone to propofol was found to be as efficacious as the mixing of lignocaine with propofol in reducing pain on injection. The fall in systolic blood pressure was significantly less in group P50 compared with groups P75 or P100. Admixture of thiopentone with propofol results in an additive hypnotic effect, a reduction in pain of injection (comparable with addition of lignocaine) and a reduced hypotensive response compared to propofol injection alone during induction.
Adolescent↗
Formation of a carcinogenic aromatic amine from an azo dye by human skin bacteria in vitro.
Azo dyes represent the major class of dyestuffs. They are metabolised to the corresponding amines by liver enzymes and the intestinal microflora following incorporation by both experimental animals and humans. For safety evaluation of the dermal exposure of consumers to azo dyes from wearing coloured textiles, a possible cleavage of azo dyes by the skin microflora should be considered since, in contrast to many dyes, aromatic amines are easily absorbed by the skin. A method for measuring the ability of human skin flora to reduce azo dyes was established. In a standard experiment, 3x10(11) cells of a culture of Staphylococcus aureus were incubated in synthetic sweat (pH 6.8, final volume 20 mL) at 28 degrees C for 24 h with Direct Blue 14 (C.I. 23850, DB 14). The reaction products were extracted and analysed using HPLC. The reduction product o-tolidine (3,3'-dimethylbenzidine, OT) could indeed be detected showing that the strain used was able to metabolise DB 14 to the corresponding aromatic amine. In addition to OT, two further metabolites of DB 14 were detected. Using mass spectrometry they were identified as 3,3'-dimethyl-4-amino-4'-hydroxybiphenyl and 3, 3'-dimethyl-4-aminobiphenyl. The ability to cleave azo dyes seems to be widely distributed among human skin bacteria, as, under these in vitro conditions, bacteria isolated from healthy human skin and human skin bacteria from strain collections also exhibited azo reductase activity. Further studies are in progress in order to include additional azo dyes and coloured textiles. At the moment, the meaning of the results with regard to consumer health cannot be finally assessed.
Benzidines↗
Molecular characterization and developmentally regulated expression of Xenopus lamina-associated polypeptide 2 (XLAP2).
Lamina-associated polypeptides 2 (LAP2alpha, beta, gamma)/thymopoietins (TPalpha, beta, gamma) are a family of proteins that are generated by alternative splicing from a single gene. These proteins have been primarily characterized in mammals. One member of this protein family, the integral membrane protein LAP2beta/TPbeta, has been localized to the inner nuclear membrane of somatic cells where it binds to chromatin and B-type lamins. By cDNA cloning we have characterized XLAP2, a Xenopus homologue of the mammalian LAP2beta. Using LAP2-specific antibodies, the Mr 68,000 XLAP2 was found to be the only member of the LAP2/TP family expressed in somatic cells and adult tissues. XLAP2 was not detected in oocytes, eggs and in early embryos up to the gastrula stage at the mRNA and protein level demonstrating that it is not synthesized from maternal mRNA. In counterpart oocytes, eggs, and embryos contained one LAP2-related integral membrane proteins of Mr 84,000. Northern blot analysis with the XLAP2 cDNA showed that a single hybridizing mRNA band of 1.8-2.0 kb was present in Xenopus somatic cells whereas two other hybridizing mRNA species of 2.8-3.0 and 0. 9-1.1 kb were present in oocytes, eggs and early embryos. All together, these results indicated that at least three distinct LAP2-related proteins might be expressed in Xenopus. The LAP2/TP protein of Mr 84,000 is present in the early embryos but its amount decreases during embryogenesis concomitant with the increase of XLAP2 in the embryo. Our results are the first description of the developmentally regulated expression of integral nuclear envelope proteins during early embryogenesis.
Amino Acid Sequence↗
Conformational analysis of ketolide, conformations of RU 004 in solution and bound to bacterial ribosomes.
A new structurally distinct class of 14-membered-ring macrolides is characterized by a keto-function instead of the cladinose sugar, well-known for its fragility even in weakly acidic media. This new class called ketolides is endowed with remarkable antibacterial activity against macrolide-resistant strains. A complete assignment of the 1H and 13C NMR spectra of RU 004 in deuteriochloroform, methanol-d4 and D2O has been made using different two-dimensional (2D) chemical-shift correlation methods. The study of ketolide-ribosome interaction has been investigated using 2D transferred nuclear Overhauser effect spectroscopy (TRNOESY). A comparison of the conformations in solution and bound to ribosomes was made with those of previous macrolides. This study can highlight some of the significant differences between RU 004 and other antibiotics.
Anti-Bacterial Agents↗
Human transferrin receptor is active and plasma membrane-targeted in yeast.
The human transferrin receptor, a type II plasma membrane protein which mediates iron transport in human cells, was expressed in the yeast Saccharomyces cerevisiae. The transferrin receptor synthesized by yeast cells was posttranslationally modified comparable to the native receptor with respect to glycosylation and dimer formation. The location of the expressed receptor in the yeast plasma membrane indicates that the targeting of this type II membrane protein shares similar mechanisms in yeast and mammalian cells. The yeast-expressed transferrin receptor showed binding activity towards its natural ligand, transferrin in an ELISA binding assay.
Cell Membrane↗
Overexpression of a cytosolic hydroxymethylglutaryl-CoA reductase leads to squalene accumulation in yeast.
The enzyme 3-hydroxy-3-methylglutaryl-co-enzyme-A (HMG-CoA) reductase is known as the rate limiting enzyme in early sterol biosynthesis in eukaryotic cells. To eliminate this regulation in the yeast Saccharomyces cerevisiae, a truncated HMG1 gene, producing a form of the enzyme that lacks the membrane-binding region (i.e. amino acids 1-552), was constructed and overexpressed in this yeast. The transformed strains accumulated large amounts of the sterol precursor squalene, while the levels of ergosterol and a number of other sterol compounds were only slightly elevated. These findings suggest that HMG-CoA reductase is not the only rate-limiting step in sterol synthesis and its overexpression cannot significantly influence this pathway beyond the sterol precursor squalene.
Cytosol↗
Hyperemesis gravidarum associated with Helicobacter pylori seropositivity.
OBJECTIVE: To test the hypothesis that infection with Helicobacter pylori is associated with hyperemesis gravidarum. METHODS: From January 1995 to November 1996 we enrolled 105 patients with hyperemesis gravidarum in a prospective study. The Helicobacter serum Immunoglobulin (Ig) G concentrations in these patients were compared with those in asymptomatic gravidas matched for week of gestation. RESULTS: Positive serum IgG concentrations were found in 95 of the 105 hyperemesis patients (90.5%) compared with 60 of 129 controls (46.5%). A chi2 test showed statistical significance (P < .001). The mean (+/-standard deviation) index percentages of the IgG titers were 74.2+/-23.6% in the hyperemesis group and 24.3+/-4.4% in the control group (P < .01, Student t test). CONCLUSION: Infection with H pylori may cause hyperemesis gravidarum.
Adolescent↗
p53 autoantibodies in patients with urological tumours.
OBJECTIVE: To determine the presence of p53 serum antibodies in patients with clinically well-defined urological cancer using a new enzyme-linked immunosorbent assay (ELISA). PATIENTS AND METHODS: The study included 73 patients with prostatic cancer, 72 with transitional cell carcinoma of the urinary tract, 37 with renal cell cancer and 16 controls with a benign disease, all of whom were tested using the ELISA for p53 autoantibodies. The specific reaction of the ELISA (positive p53 antibody titre) was confirmed by Western Blot analysis. RESULTS: Thirteen patients with cancer and one control patient (7.6% overall) were positive for p53 autoantibodies. The sensitivity of the test was low, whereas the specificity was remarkably high. Surprisingly, 9 of the 13 p53-positive patients died within a median of 3.7 months (range 2-6) and the one positive control patient died of undetected lung cancer. There was no significant correlation of p53 antibody positivity with clinical stage or tumour-specific differences. CONCLUSIONS: The expression of p53 autoantibody seems to be a very late but significant event in urological tumour development, with the worst outcome (tumour-specific death) within a few weeks of developing positivity. In histopathologically heterogeneous tumour entities, p53 autoantibodies might be independent prognostic factors in patients with urological cancers.
Autoantibodies↗