[Sterilization of mentally retarded girls].
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Biomedical subjects
Publications and source records attributed to K Müller.
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Inhibition of glucose-6-phosphate dehydrogenase (G6-PDH) by dithranol (anthralin, CAS 480-22-8) has been studied in the presence of catalase, superoxide dismutase (SOD) and various scavengers of active oxygen species. Most scavengers were found to be either inhibitors of G6-PDH by themselves or simply without effect. The combined addition of catalase and SOD as well as the heat-denatured enzymes and the oxygen radical scavengers alpha-tocopherol and salicylic acid markedly reduced the inhibitory effect of dithranol. The direct exposure of G6-PDH to active oxygen species led to different results. When liberated from a water-soluble naphthalene endoperoxide, singlet oxygen was without effect whereas photosensitization with methylene blue resulted in a total loss of enzyme activity. Experiments under anaerobic conditions revealed that this inhibition was accomplished by the triplet state of the sensitizer. Superoxide anion radical was highly effective at concentrations corresponding to the amount of that produced by a 10 mumol/l dithranol solution. In contrast, hydroxyl, alkylperoxyl and alkoxyl radicals were all less efficient. H2O2 and alkylhydroperoxides did not alter the enzyme activity. The results suggest that .O2- is the potent species towards G6-PDH, if dithranol acts through formation of active oxygen species.
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The nucleotide sequences of two non-allelic histone H2A-H2B gene loci of the green alga Volvox carteri have been determined. Each locus contains a divergently arranged H2A-H2B gene pair. The encoded proteins differ in one (H2A) and 16 positions (H2B), respectively. The coding regions are separated by short intercistronic segments (256 bp and 298 bp) containing TATA boxes and a central tandem repeat of a conserved 20-bp element as the putative histone-specific transcription signals. The 3'-untranslated regions exhibit a characteristic 3'-palindrome and weakly conserved spacer elements. Transcription in one gene locus was shown to initiate 48 bp upstream from H2A and 59 bp upstream from H2B. Contrary to higher plants, V. carteri histone mRNAs are nonpolyadenylated. S1 mapping and Northern-blotting experiments indicated that V. carteri histone mRNAs are terminated at the 3'-palindrome by the same mechanism that operates in vertebrates and sea urchins.
Phorbol ester-induced promotion of initiated NMRI mouse skin keratinocytes to papillomas could be largely prevented when nicotinamide-like inhibitors of poly(ADP-ribose)polymerase (nicotinamide, benzamide, 3-aminobenzamide) were applied simultaneously with 12-O-tetradecanoylphorbol-13-acetate (TPA). A similar suppression of tumor promotion by nicotinamide analogues was demonstrated in clone 41 JB6 epidermal cells which are promotable by TPA to anchorage-independent growth. The antipromotion effect of nicotinamide analogues, however, does not appear to come about by an inhibition of poly(ADP-ribose)polymerase. Acid analogues of nicotinamide, such as benzoic acid or 3-aminobenzoic acid which do not inhibit the polymerase, showed antipromotion activity similar to that of their corresponding amides. It could also be ruled out that these antipromoters mediate their effect on keratinocytes by a cytostatic action, by scavenging the promoter TPA in a chemical reaction, or by inhibiting protein kinase C. In initiated mouse skin, nicotinamide analogues strongly suppressed TPA-induced accumulation of inflammatory cells and vascular permeability, while epidermal hyperplasia was not significantly affected.
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Lys601 in NADPH-cytochrome P-450 reductase is modified by reductive alkylation with pyridoxal 5'-phosphate (pyridoxylation). Lys601 is protected against modification by the cosubstrate NADP(H).
These studies are an attempt to gain better insight into the pharmacophore requirements of urease. On the basis of published information on this enzyme (EXAFS, amino acid sequence, essential groups at the active site) a hypothetical nickel-tripeptide complex, as preliminary substitute for the urease active site was modeled using computer-aided molecular modeling techniques. The results suggest two alternative docking modes of urea and reaction intermediates, corresponding to two different reaction mechanisms. Both binding modes are compatible with the docking of known potent inhibitors such as selected hydroxamic acids and phosphorodiamides. The results can be used to help in the design of new potential inhibitors of urease.
Southern blot analysis of Volvox carteri DNA indicated the presence of a single actin gene; the nucleotide sequence of that gene is reported here. In comparison with plant animal and fungal actins, the derived primary structure of 377 amino acids is highly conserved yielding similarity values of 79% to 94% (including non-identical conservative exchanges). In contrast, the intron structure of the gene is highly unusual: in addition to one intron in the 5' untranslated region (ten nucleotides upstream of the initiator ATG), it has eight introns in the coding region, only three of which are in locations where introns have previously been reported. Transcription starts 26 nucleotides downstream of the putative TATA box and 70 nucleotides downstream of a conspicuous CCAAT motif. A potential polyadenylation signal, TGTAA, is located 366 nucleotides downstream of the terminator TAA. Northern hybridization indicates that the actin gene is transcribed throughout the Volvox life cycle with only a slight depression during the release of juveniles from mother spheroids. This pattern of gene expression suggests that actin may assume various functional roles in the differentiation and growth of Volvox.
A new quadruple blood bag system for collection of platelet concentrates is described. The principle modification consists of a smaller (150 ml) buffy coat bag in conjunction with SAG-mannitol for red cell preservation. Platelet yield and function were comparable to conventional techniques, leukocyte contamination was lower (1.7 +/- 1.3 x 10(7) per unit). The system is recommended for specialized institutions with a high demand of blood components.
The solubilization of multilamellar egg yolk lecithin liposomes by sodiumtaurodeoxycholate in aqueous phase was studied by ultrafiltration as a function of time, bile salt and cholesterol concentration. The corresponding equilibrium states were analysed. Complete solubilization was achieved at total bile salt/lecithin molar mixing ratios of approximately 5. The minimum ratio to start solubilization was 0.1, corresponding to a free bile salt concentration of only 5% of the critical micelle concentration (CMC). Mean equilibrium constants for the partition of bile salts between non-filterable aggregates and filterable mixed micelles and also the free bile salt concentration were determined. Sodiumtaurodeoxycholate had a higher affinity for small mixed micelles than for lamellar mixed aggregates especially in the presence of cholesterol, which reduces the degree and rate of the solubilization process. A non-homogeneous distribution of bile salts in the lipid phase was detected at low bile salt concentrations.
3-Deazaaristeromycin and 3-deazaadenosine (3DA-Ado) both interfere with the methylation of RNA, but only 3DA-Ado is metabolized to the corresponding homocysteine derivative. In contrast to 3-deazaaristeromycin, 3DA-Ado inhibits the synthesis of late influenza A virus proteins in chicken embryo cells (CEC), while it causes an overproduction of early proteins and of the nonstructural proteins NS2 and M2. Only the former effect of 3DA-Ado can be reversed by concomitant addition of adenosine, but not by guanosine. 3DA-Ado acts only early in the infectious cycle and, after removal of the drug, its effect on the yield of infectious virus is reversible. It can be significantly enhanced by homocysteine thiolactone. Except for the M gene, synthesis of viral mRNA is not significantly affected by 3DA-Ado. We conclude that 3DA-Ado acts via its homocysteine derivative by interfering with a specific post-transcriptional modification of viral mRNA and on splicing of specifically the M mRNA. In L-cells influenza viral protein synthesis is comparable to that in CEC in the presence of 3DA-Ado in that there is only little HA and M1 synthesized, and a severe overproduction of NS2 is observed. Under the experimental conditions 3DA-Ado has no inhibiting effect on the replication of other RNA viruses like Newcastle disease virus, Semliki Forest virus, or West Nile virus whose RNA is not methylated, since they do not have a nuclear phase during replication.
The photooxidation of the antipsoriatic drug anthralin (1,8-dihydroxy-9-anthrone) has been studied by several kinetic techniques, including direct observation of 1O2 (1 delta g) luminescence at 1.27 microns. The rate of deactivation of 1O2 increases at higher pH, demonstrating that the trihydroxyanthracene anion is the reactive species. Direct determination of the rate constant of 1O2 deactivation (kR + kQ) in deuterated buffer systems by luminescence quenching gave a value of 3.0 x 10(8) M-1 s-1 for the anion; the neutral anthrone is unreactive. The rate constant for the neutral anthrone in benzene-d6 is 2.8 x 10(4) M-1 s-1. Competition experiments with tetramethylethylene in acetonitrile gave a rate constant for reaction alone (kR) of 2.1 x 10(8) M-1 s-1 for the anion.
Recent studies have suggested that vitamin D3 may have an immunoregulatory role in vitro. The vitamin D3 metabolism in 35 patients with primary Sjögren's syndrome was investigated by measuring blood concentrations of 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25-(OH)2D3) and 25-hydroxyvitamin D3 (25-OHD3), as well as phenotypes and blood concentrations of Gc globulin, the main vitamin D3 binding protein in the blood. 25-OHD3 concentrations were diminished, but those of 1 alpha,25-(OH)2D3 were normal. There was no significant difference between the distribution of Gc phenotypes in the patients with primary Sjögren's syndrome and normal controls. Likewise, blood concentrations of Gc globulin corresponded to normal values. Among patients with increased concentrations of IgM rheumatoid factor there was a significant negative correlation between the serum titres of IgM rheumatoid factor and 25-OHD3 concentrations.
It has repeatedly been shown that platelet concentrates (PC) can be prepared from buffy coat in guadruple Saline(S)-Adenin(A)-Glucose(G)-Mannitol(M) (SAG-M) systems. Their in vivo and in vitro quality was reported to be excellent and their contamination with leucocytes was 10-20 times lower than in PC prepared from platelet rich plasma. We have confirmed these observations (unpublished results). One particular technical problem which we encountered was the appearance of folds in the satellite bag during the second centrifugation step rendering the purity of the PC quite unpredictable. In collaboration with Biotrans, we have developed a modified quadruple bag (733861100) including a special insert (Heraeus Christ, Osterode, FRG) for the centrifugation rotor which has proved advantageous over existing systems and will be briefly described.
One hundred platelet concentrates, fifty prepared from buffy coat and fifty prepared from platelet-rich plasma were examined. In platelet concentrates from buffy coat a lower leukocyte contamination (1.4 +/- 1.2 x 10(7) vs 13.2 +/- 15 x 10(7], a significant higher ATP content (6.3 +/- 1.7 mmol/10(14) platelets vs 3.9 +/- 1.9 mmol/10(14) platelets) and a better response in ADP- or collagen-induced aggregation could be determined during storage of five days. Our results indicate that preparation of platelet concentrates from buffy coat is preferable to their preparation from platelet-rich plasma.
As a result of investigations into the diagnostic validity of selected haematologic-morphological and clinical-chemical test factors of iron metabolism in the diagnosis of hypochromic anaemia, the examined test faktora are differently evaluated as individual parameters and in their combination. 1. Haematocrit (PCV) is equal to the determination of haemoglobin concentration as a search parameter. 2. The number of reticulocytes, copper and zinc as well as caeruloplasmin have a separating effect as individual parameters on the examined classes of iron deficiency and tumour and infect anaemia. 3. Iron has no value as a individual parameter. It is only in combination with TEBK and the haematologic test factors that is has a diagnostic value. 4. In contrast, ferritin as an individual parameter is of primary importance and should be used extensively in the laboratory diagnosis of hypochromic anaemia. 5. TEBK and transferrin may be supposed to be equal in their diagnostic value. 6. When used in combination, haemoglobin, MCV, TEBK, Transferrin, and ferritin have effective separating function. They permit hypochromic anaemia to be widely assigned to one or another kind of the examined classes.
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