Packing the perineal wound with a resorbable (polyglactin) net in difficult cases following abdomino-perineal excision of the rectum.
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Humans↗
Biomedical subjects
M Schweiger
Publications and source records attributed to M Schweiger.
Asbestos: a chronology of its origins and health effects.
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Asbestosis↗
[Malignant somatostatinoma--diagnosis after 6 years].
UNLABELLED: Early symptoms of malignant somatostatinoma with dyspeptic complaints, moderate diabetes mellitus and cholecystolithiasis are the reason of primary treatment of these patients by surgeons. CASE REPORT: In a 34-year old patient with typical anamnesis of cholecystitis and moderate diabetes mellitus liver metastases were seen during laparotomy. In the beginning the metastases were mistaken for hepatocellular carcinoma histologically. There was no deterioration until June 1988 when a high-grade stenosis of the duodenum has developed. Now a malignant somatostatinoma was diagnosed histologically and confirmed by immunohistology. Somatostatinomas are generally diagnosed by repeated measures of increased plasma SLI associated with decreased insulin, glucagon, pancreatic-polypeptide (PP) and vasoactive-intestinal-peptide (VIP). In normally or moderately increased plasma SLI concentrations provocation with tolbutamid may be helpful. Treatment should remove most of the tumor by surgical intervention, while chemotherapy must be less pronounced.
Adenoma, Islet Cell↗
Clinical and biochemical studies in three patients with severe early infantile Cockayne syndrome.
We present clinical and biochemical data from three patients with severe Cockayne syndrome (CS) of very early onset. Unlike in classic CS, signs became evident in the first weeks of life and led to unusually early death. Fibroblasts from two of the patients showed a complete defect of the repair of UV-induced thymine dimer lesions. They were unable to remove thymine dimer lesions from their DNA, had a severe reduction of the RNA synthesis rates after UV irradiation, and showed no reactivation of an UV-inactivated indicator gene and no DNA recondensation after UV irradiation. DNA repair investigated in these two fibroblast cell strains resembled that of xeroderma pigmentosum cells of complementation group A. In contrast, fibroblasts from the third patient showed the same in vitro repair characteristics as classic CS cells.
Cell Survival↗
Human nuclear NAD+ ADP-ribosyltransferase: localization of the gene on chromosome 1q41-q42 and expression of an active human enzyme in Escherichia coli.
The gene for human nuclear NAD+ ADP-ribosyltransferase [NAD+:poly(adenosine diphosphate D-ribose) ADP-D-ribosetransferase, EC 2.4.2.30; pADPRT] was localized to chromosome 1 at q41-q42 by in situ hybridization with a pADPRT-specific cDNA probe. Expression of a pADPRT cDNA under control of the lac promoter in Escherichia coli induces the synthesis of a group of related proteins that were immunoreactive with pADPRT antibody and that had catalytic properties very similar to those of the human enzyme. Purification of this enzymatic activity was performed essentially as described for the human enzyme. The Km, pH optimum, optimal reaction temperature, and inhibition by 3-aminobenzamide and 3-methoxybenzamide were found to be similar for the recombinant and the human enzymes. The purified recombinant enzyme consists of two major proteins of Mr 99,000 and Mr 89,000. Both proteins show pADPRT activity in activity gel analysis with [32P]NAD+ as substrate. Microsequencing of these two proteins isolated by denaturing gel electrophoresis and deletion mutagenesis of the pADPRT expression plasmid shows that the Mr 99,000 and Mr 89,000 proteins derive from initiation of translation at internal translational start signals located within the pADPRT cDNA.
Amino Acid Sequence↗
Human nuclear NAD+ ADP-ribosyltransferase(polymerizing): organization of the gene.
Human nuclear NAD+: protein ADP-ribosyltransferase(polymerizing) [pADPRT; poly(ADP-ribose)poly-merase; EC 2.4.2.30] is a DNA-dependent protein-modifying enzyme composed of several domains important for DNA binding, automodification, and NAD binding. We report that the human pADPRT gene is 43 kb in length and is split into 23 exons. All the intron-exon boundaries correspond to a canonical splice consensus sequence. Each of the four metal coordinating sites putatively forming the two zinc fingers of the DNA-binding domain is encoded separately. The automodification domain and the NAD-binding domain are coded for by 4 and 12 exons, respectively.
ADP Ribose Transferases↗
Ultrastructure of Fanconi anemia fibroblasts.
Employing indirect immunofluorescence and conventional electron microscopy, gross nuclear aberrations were observed in cultured interphase fibroblasts derived from a patient suffering from Fanconi's anemia (FA). Such aberrations were predominantly expressed in cells at high passages between 28 and 34. The structure of the nuclei appeared compound in nature, often consisting of two to three nuclear fragments connected to each other by thin nuclear bridges containing chromatin and nuclear lamin material. In other cases, the nuclei appeared lobed or budded but the cells did not contain distinct nuclear fragments. Chromatin was conspicuously absent from some nuclear lobes, revealing empty, cage-like structures comprising nuclear lamin material. Micronuclei were often abundant in the perinuclear cytoplasm but in some instances they appeared to be composed of chromatin lacking a delineating nuclear lamin matrix. Residual cytoskeletons examined by whole-mount electron microscopy revealed a network of intermediate filaments (IFs) within FA fibroblasts forming a bridge between the plasma membrane and the nucleus or its major fragments. In addition, there were thinner, 3-4 nm filaments connecting individual IFs with the surface of the nucleus. Micronuclei that were not connected to the main nuclear body, but which were delineated by a distinct lamina and possessed nuclear pores, did not appear to be anchored to the IF network. Multinuclearity, nuclear fragmentation, irregular chromatin distribution and inter-nuclear chromatin/lamin bridges might result from a failure in the redistribution of chromatin to sister nuclei, incomplete cytokinesis and proliferation of nuclear envelope material. These phenomena point to precocious aging of FA fibroblasts and may occur as a consequence of spontaneous damage to the sister chromatids or through the action of DNA-toxic agents.
Anemia, Aplastic↗
Radiation sensitivity of Down's syndrome fibroblasts might be due to overexpressed Cu/Zn-superoxide dismutase (EC 1.15.1.1).
Trisomy 21 (Down's syndrome, DS) is the most frequent chromosomal aberration. Triplication of a small region of chromosome 21, the fragment 21q22 is sufficient to cause the DS phenotype including immunodeficiency, premature aging, neurodegenerations, mental retardation and an increased risk of leukemia. Chromosomal aberrations caused by X-ray irradiation were observed in DS lymphocytes and DS fibroblasts, but the correlation to cell death or repair deficiency was not clear. We approached this problem and report here on a profound X-ray repair deficiency of DS cells. With a colorimetric viability assay we observed an UV sensitivity of DS fibroblasts at doses beyond 14 Jm-2 but no significant X-ray sensitivity. By the nucleoid sedimentation technique, a deficient restoration of nucleoids in DS cells after X-ray irradiation was demonstrated. The same features apply for cells, which contain an overexpressed Cu/Zn-superoxide dismutase (SOD-1) gene. Radiation sensitivity of DS cells and SOD-1 overexpressing cells resemble those of ataxia telangiectasia (AT) fibroblasts. Additionally, DS and AT cells exert lack of inhibition of DNA synthesis after X-ray irradiation.
Cell Line↗
The primary structure of human ribonuclease/angiogenin inhibitor (RAI) discloses a novel highly diversified protein superfamily with a common repetitive module.
Immunological screening of a lambda gt11 library, constructed from HeLa mRNA, yielded several ribonuclease/angiogenin inhibitor (RAI) cDNA clones containing 900-bp inserts. Northern blot analysis revealed that the length of the RAI mRNA is approximately 1.9 kb. Construction and screening of a eukaryotic cDNA expression library (HeLa) containing preferentially complete cDNA inserts led to the isolation of a full length clone. The complete nucleotide sequence was determined. The C-terminal amino acid sequence deduced from the cDNA is identical to the peptide sequence obtained from a CNBr fragment of RAI, confirming the identity of the clone. The deduced primary structure of RAI consists of eight homologous tandem repeats with remarkable periodicity of leucine and cysteine residues. Each repeat is derived from the duplication of a leucine-rich 28-amino-acid module. This prototype module is closely related to a repetitive 24-amino-acid motif of unclear function, previously found in proteins involved in important biological processes such as blood coagulation, embryonic development, cell morphogenesis and signal transduction. Although homologous, the RAI modules show distinct differences in length and amino acid composition to the modules of this group of proteins, demonstrating their high potential of variability, necessary for adaptation to very diverse roles. Based on our results we propose that these repetitive modules are a common structural feature of a novel protein superfamily whose members exert their function by highly specific protein-protein interactions.
Amino Acid Sequence↗
Caloric intake, stress, and menstrual function in athletes.
The cause of menstrual disturbance in athletes is still debated. Apart from the acute and chronic effects of exertion, other associated behavioral variables are suspected to play a key role. A longitudinal study with frequent blood sampling was undertaken to link information about nutrition and stress with a quantitative assessment of endocrine menstrual function in 18 endurance-trained athletes and 25 age-matched, nonathletic women. Four athletes did not show hormonal signs of follicular development. The 14 athletes with cyclic gonadal function did not differ from controls with regard to estradiol concentrations during the follicular phase and at midcycle. During the luteal phase, however, they showed significantly reduced areas under the estradiol and progesterone curves. Caloric intake, as assessed by nutritional diaries, correlated positively with the area under the progesterone curve during the luteal phase (rs = 0.70, P less than 0.01). Ratings of subjective stress in the area "partner, family, friends" correlated negatively with the luteal progesterone area (rs = 0.80; P less than 0.01). Data support the hypothesis that nutrition and stress may play a critical role in the genesis of menstrual disturbance in athletes.
Adult↗
ADP-ribosyltransferase from Helix pomatia. Purification and characterization.
ADP-ribosyltransferases from several higher eukaryotes have been purified and characterized, but little is known about ADP-ribosyltransferases in lower eukaryotes. We have purified an ADP-ribosyltransferase (EC 2.4.2.30) from Helix pomatia. The enzyme has an apparent Km of 26.7 microM. Optimal conditions for the enzyme reaction are 17.5 degrees C and pH 8. The time course is linear during the first 10 min of the reaction. The enzyme is capable of poly-ADP-ribosylation. The most highly purified preparation shows one major band at an Mr of 75,000 on electrophoresis in an SDS/polyacrylamide gel, with minor bands at Mr 115,000 and 155,000. Re-activation of SDS/polyacrylamide gels in situ shows the 75,000-Mr band to be enzymically active and additional active bands with Mr values of 115,000, 90,000 and 87,000 respectively. The 115,000-Mr and 75,000-Mr bands cross-react with a polyclonal affinity-purified antiserum against human ADP-ribosyltransferase. Like enzymes from higher eukaryotes, the activity from Helix pomatia is inhibited by thymidine, theophylline, theobromine nicotinamide, 3-methoxybenzamide and 3-aminobenzamide, and is dependent on histone and DNA.
Animals↗
Identification, purification, and characterization of Escherichia coli virus T1 DNA methyltransferase.
An Escherichia coli virus T1-induced DNA methyltransferase was identified by activity gel analysis in homogenates of infected E. coli DNA-adenine-methylation-deficient strains. Although the Mr of this protein (31,000) is in the same range as that of the E. coli DNA adenine methyltransferase, the two proteins are not closely related; the E. coli dam gene does not hybridize with T1 DNA. Selective conditions for measurement of the T1 activity were developed, and the enzyme was purified to functional homogeneity, as shown by activity analysis in polyacrylamide gels. Requirements for optimal activity of the viral enzyme were determined to be pH 6.9, ionic strengths below 0.1 M KCl, and a temperature between 40 and 43 degrees C. The Km for S-adenosyl-L-methionine is 4.9 microM. The purified T1 DNA methyltransferase is capable of methylating adenine in 5'-GATC-3' sites in vitro.
DNA (Cytosine-5-)-Methyltransferases↗
The Fritz-Lipmann lecture. DNA repair in human cells. Biochemistry of the hereditary diseases Fanconi's anaemia and Cockayne syndrome.
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Acetyltransferases↗
ADP-ribosyltransferase is highly conserved: purification and characterization of ADP-ribosyltransferase from a fish and its comparison with the human enzyme.
Covalent modification of proteins by ADP-ribosylation is a major mode of protein regulation in eukaryotic cells. ADP-ribosyltransferases have been characterized from mammals but little is known about these enzymes in lower vertebrates. We purified an ADP-ribosyltransferase (E.C. 2.4.2.30) from trout (Salmo trutta faris) by affinity chromatography and characterized it. The 11,700-fold purified activity shows a major protein band at a molecular mass of 75,000 kDa in a SDS-polyacrylamide gel. In situ reactivation of SDS gels showed the 75,000 kDa protein to be enzymatically active, and additional enzymatically active bands at molecular masses of 115,000, 90,000 and 87,000 kDa, respectively. The enzyme is capable of poly-ADP-ribosylation. It crossreacts with affinity purified antibodies raised against human poly(ADP-ribose)synthetase and, except for the temperature optimum, its properties strongly resemble the mammalian enzymes, indicating the conserved character of nuclear ADP-ribosyltransferases. The trout enzyme is DNA- and histone-dependent, has an optimal pH between 8 and 9 and an apparent Km for NAD+ of 24 microM. The temperature optimum is 10 degrees C compared with 25 degrees C for the human enzyme. Known ADP-ribosyltransferase inhibitors also inhibit the enzyme from trout.
Animals↗
Diet-induced menstrual irregularities: effects of age and weight loss.
Luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), and progesterone (P) levels were followed in 22 healthy, normal-weight women (aged 19 to 30 years) for a control and a diet menstrual cycle. During the diet cycle, they lost weight on a high-carbohydrate, vegetarian, 1000-calorie diet. During the control cycle, luteal phase in 5 subjects failed to meet the criteria: length greater than or equal to 8 days and P maximum greater than or equal to 6 ng/ml; during the diet cycle, the number of subjects who failed to meet these criteria was 14 (chi-square test, P less than 0.02). No evidence of follicular phase disturbance was observed during the diet. Age and weight loss significantly changed parameters of the diet luteal phase: length and area under LH, FSH, E2, and P curves. Generally, hormone plasma concentrations during the luteal phase were lower the younger the age and the greater the weight loss.
Adult↗
Interferon-gamma-induced degradation of tryptophan by human cells in vitro.
Several human cells were investigated for their ability to degrade tryptophan and to synthesize neopterin upon induction by interferon-gamma (500 units/ml for 48 h). Concentrations of tryptophan, kynurenine, 3-hydroxykynurenine, anthranilic acid, 3-hydroxyanthranilic acid, 7,8-dihydroneopterin and neopterin were assessed in the culture supernatants by HPLC. Fibroblasts, A-22 arachnoidea, HK-2351 scalp, T-2346 meningeom and HeLa cervical carcinoma cells but not HL-60 promyelocytic leukaemia cells were found to degrade tryptophan upon induction by interferon-gamma. Tryptophan is converted to kynurenine by fibroblasts, A-22 arachnoidea and HK-2351 scalp cells and to kynurenine and anthranilic acid by HeLa cervical carcinoma and T-2346 meningeom cells. Kynurenine and anthranilic acid always make up more than 82% of the tryptophan degraded. None of these cells synthesizes 3-hydroxyanthranilic acid, 3-hydroxykynurenine, 7,8-dihydroneopterin or neopterin. Human macrophages form 3-hydroxyanthranilic acid and neopterin, but not 3-hydroxykynurenine, beside kynurenine and anthranilic acid upon activation by interferon-gamma. These data indicate that several human cells can be induced by interferon-gamma to degrade tryptophan. The interferon-gamma induced synthesis of 3-hydroxyanthranilic acid and neopterin, however, appears to be restricted to human macrophages. A hypothesis explaining these findings is presented.
Biopterins↗
Isolation of a cDNA clone for human NAD+: protein ADP-ribosyltransferase.
NAD+:Protein ADP-ribosyltransferase (EC 2.4.2.30) (ADPRT) was purified from human placenta by affinity chromatography. With the purified enzyme specific antibodies were raised and partial amino acid sequences were determined. To one of the amino acid sequences corresponding oligonucleotides were synthesized. A sized HeLa lambda gt11 cDNA library was constructed and screened. Positive clones were characterized to be ADPRT specific by immuno- and hybridization techniques. Clone ADPRT-G8 reacted with affinity chromatographically purified specific antibodies and with two specific oligonucleotides. The DNA of this clone detected an mRNA of about 4 kb, sufficient in size to code for the ADPRT with an Mr of 116,000. Partial sequence analysis of this clone confirmed its identity by revealing sequences which code for peptides which were found in cyanogen bromide (CNBr) fragments of the purified enzyme. The ADPRT-G8 clone was characterized with respect to its restriction pattern. The cloned ADPRT cDNA now opens the possibility to investigate the role of this enzyme in control of cellular functions.
ADP Ribose Transferases↗
[Feasibility of methods of outpatient preparation for proctologic examination. Comparison of phosphate and sorbit enemas in a randomized double-blind study].
Phosphate and sorbite enemas for preparing a patient for rectoscopy and flexible endoscopy were compared in a randomised double-blind study on 60 patients. Side effects were low and equally rare in both groups of patients. There was no statistically significant difference in the cleansing quality of both enemas. Phosphate enemas produced reliable onset of action in a significantly shorter time, and the cleansing depth was also significantly better.
Adolescent↗