[Generalized argyria caused by targesin-containing drug used for stomach complaints].
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Biomedical subjects
Publications and source records attributed to M Müller.
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The increasing number of therapeutic modalities and growing experience in the treatment of gallstones involve continuous changes in the indications and contraindication of each method. The advantages of the conservative, non-surgical and interventional procedures are that patients can become free of symptoms and stones without the use of general anaesthesia or surgery, however, there is the risk of recurrence. On the other hand, invasive surgical methods provide a definitive solution to the problem by removal of the focus, eliminating the risk of recurrent disease. To our opinion, it is important to offer as many therapeutic modalities possible to be selected as individual treatment by patients and physicians.
We report on a microcephalic, growth-retarded newborn girl without major anomalies who has chromosome instability in lymphocytes and fibroblasts. Frequent involvement of bands 7p13, 7q34, 14q11, and 14q32 suggested the diagnosis of ataxia telangiectasia (AT) or a related disorder. Supportive evidence was radioresistant DNA synthesis in fibroblasts and radiation hypersensitivity of short-term lymphocyte cultures. Follow-up for nearly 4 years showed largely normal development, and no signs of telangiectasia, ataxia, or immunodeficiency. Serum AFP levels turned from elevated at age 5 months to normal at age 2 years. We propose that our patient belongs to the expanding category of "AT-related" genetic disorders, probably to the Nijmegen breakage syndrome.
Whole-cell, current clamp, single channel recordings and 86Rb+ flux techniques were used to show that phenothiazines inhibit ATP-sensitive K+ channels (KATP) in HIT-T15 beta-cells. Chlorpromazine inhibition was observed when KATP channels were activated by ATP depletion or by direct treatment with a classical KATP channel opener, diazoxide. The order of potency of the phenothiazines tested was chlorpromazine greater than triflupromazine greater than fluphenazine greater than trifluopromazine with IC50 values of 1, 4, 6 and 20 microM, respectively. The inhibition was reversible.
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As one of the causes of sudden cardiac death, recurrent ventricular arrhythmia represents a potentially life-threatening rhythm disorder. amiodarone is an effective anti-arrhythmic drug, the effectiveness of which is based on a prolongation of the action potential and thus a lengthening of the refractory period. In a multicenter, noncontrolled observational study of 482 patients aged between 21 and 89, it was found that amiodarone effectively suppressed life-threatening or crippling arrhythmias in a majority of the patients, even when they had previously been unresponsive to other anti-arrhythmic agents. Physical performance improved under the treatment. An analysis of the side effects observed revealed good tolerance at a low maintenance dose.
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The structure of a mutant Antennapedia homeodomain, Antp(C39----S), from Drosophila melanogaster was determined using a set of new programs introduced in the accompanying paper. An input dataset of 957 distance constraints and 171 dihedral angle constraints was collected using two-dimensional n.m.r. experiments with the 15N-labeled protein. The resulting high quality structure for Antp(C39----S), with an average root-mean-square deviation of 0.53 A between the backbone atoms of residues 7 to 59 in 20 energy-refined distance geometry structures and the mean structure, is nearly identical to the previously reported structure of the wild-type Antp homeodomain. The only significant difference is in the connection between helices III and IV, which was found to be less kinked than was indicated by the structure determination for Antp. The main emphasis of the presentation in this paper is on a detailed account of the practical use of a novel strategy for the computation of nuclear magnetic resonance structures of proteins with the combined use of the programs DIANA, CALIBA, HABAS and GLOMSA.
Systemic lupus erythematosus is an autoimmune disease, characterized by high titers of autoantibodies against many cell-membrane and intracellular antigens. Polyclonal B cell activation and alterations in the T cell compartment have been described. The present report deals with the organ-associated macrophage (M phi) system of two lupus-prone mouse strains (NZB/W and MRL lpr/lpr) and demonstrates that in both mouse strains the M phi compartment of liver and spleen is clearly expanded. In the liver the number of F 4/80+ M phi is strongly elevated. In addition, presence of early M phi precursors and of extramedullary organ-associated monocyte proliferation in response to colony-stimulating factor (CSF) is documented in liver and spleen of these mice. Further, in normal animals during the first two weeks of life extramedullar monocytopoiesis is present in liver and spleen, which is then down-regulated in the third week of life. In the two lupus-prone mouse strains down-regulation does not occur but extramedullar monocyte proliferation is sustained at high level throughout life time. As possible correlates for the expansion of the M phi system elevated CSF-1 mRNA levels are demonstrated in kidney, spleen and liver of NZB/W mice and elevated CSF serum levels are documented in MRL lpr/lpr mice. The possible contribution of the expanded M phi system to B and T cell dysregulation is discussed.
Extracorporeal procedures for selective removal of low-density lipoproteins have become a promising new approach for treatment of severe familial hypercholesterolemia. We tested efficacy and safety of a new LDL apheresis system by using two dextran sulfate cellulose adsorbents (Liposorber LA 15TM from Kanegafuchi) under the control of an automatic column-regenerating unit for continuous alternate adsorption and desorption. Plasma was taken from a continuous-flow blood cell separator (model IBM/Cobe 2997) allowing an extracorporeal circuit from one cubital vein to another. A 57-year-old male with drug-resistant heterozygous familial hypercholesterolemia accompanied by moderate hypertriglyceridemia and severe coronary artery disease has been treated every 2 weeks for 3 months so far. Treatment of 4-5 liters of plasma resulted in a mean decrease of total cholesterol from 355 to 111 mg/dl (9.20 to 2.88 mmol/l), of LDL cholesterol from 272 to 49 mg/dl (7.05 to 1.53 mmol/l), and of apolipoprotein B from 175 to 44 mg/dl. HDL cholesterol, apolipoprotein A-I, and other plasma proteins did not substantially change apart from hemodilution. No side effects were seen. This new technique of LDL apheresis represents a very effective and safe method for treatment of drug-resistant familial hypercholesterolemia without or with concomitant hypertriglyceridemia.
Structural information on the surface of biological specimens can be resolved within molecular dimensions by "in-lens" field emission scanning electron microscopes when cryo-methods are used to adequately preserve the native state of the specimen. The visual definition of molecular surface structures depends largely on the metal coating. The thickness of the coating, as well as the temperature at which it is deposited, are among the most important parameters affecting visual definition. These were evaluated on T4 polyheads and T4D phages using chromium double-axis rotary shadowing (DARS). Micrographs of optimally DARS coated T4 polyheads and T4D phages were compared with chromium planar-magnetron sputtering (PMS) and unidirectional shadowing with platinum/carbon. Metal deposition was carried out at low temperatures during all three procedures. Optimal visual definition of structural details on the surface of DARS coated T4 polyheads and T4D phages (capsomeres of T4 polyheads and their subunits with diameters of 8 and 3 nm; T4D phage tail fibres with a thickness of 3 nm) is achieved at a thickness of the chromium film greater than the minimum required for metal film coalescence. Chromium DARS coating at room temperature resulted in poor structural definition, whereas DARS at specimen temperatures of -85 degrees C and -150 degrees C, with the chromium thickness optimized for each temperature, yielded good visual detail of polyhead substructures. The visual definition was slightly reduced when DARS coating was carried out at a specimen temperature of -250 degrees C. Adequate structural visibility of T4D phage and T4 polyhead surface structures was achieved with the three coating techniques tested.(ABSTRACT TRUNCATED AT 250 WORDS)
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A 1420 bp genomic fragment (lambda-hor1-17) encompassing a Hor-1 gene encoding a C-hordein polypeptide is presented. The deduced amino acid sequence is 261 residues long. It comprises a 20 amino acid signal peptide, unique NH2- and COOH-terminal regions and a coding region comprised of pentapeptide (PQQPY) and octapeptide (PQQPFPQQ) repeat motifs. The 431 bp of 5' non-coding region contains a 'TATA box' at -105, a 'CACA box' (-181 to -201) and a -300 prolamin element. In the 3' non-coding region there are two putative polyadenylation signals located 88 and 142 bp downstream of the stop codon. The structure of lambda-hor1-17 is compared with that of another gene (lambda-hor1-14) encoding a C-hordein polypeptide, which contains an amber codon interrupting the ORF. A functional assay in which the 5' non-coding regions of the two genes were fused to the beta-glucuronidase (GUS) gene demonstrated that both genes were transcriptionally active and that circa 430 bp of the C-hordein promoters were sufficient to drive the expression of the GUS gene in developing barley endosperms. It also demonstrated that both promoters had transcriptional efficiencies comparable with that of the 35S CaMV promoter. The in vitro translation of the coding region of lambda-hor1-14 in the wheat germ system showed that the premature stop codon could be partially suppressed. The suppression was also demonstrated in a transient expression assay in vivo using isolated barley endosperms.
Anesthetized Mongolian gerbils were subjected to 5-min ischemia and 8 h of recirculation. Vibratom sections were taken for studying changes in ornithine decarboxylase (ODC) immunoreactivity using an antiserum to ODC, and tissue samples were taken for measuring ODC activity. After 5-min ischemia and 8-h recirculation ODC activity increased 11.5-, 5.9-, and 7.9-fold in the cerebral cortex, striatum and hippocampus, respectively (P less than or equal to 0.05 to 0.01). In the cortex, striatum and hippocampus of control animals immunoreactivity was low but clearly above the detection limit. The reaction was confined to neurons. After 5-min ischemia and 8-h recirculation a sharp increase in immunoreactivity was observed confined to neurons, indicating that the postischemic activation of polyamine metabolism is a neuronal response to ischemia. The immunoreactivity was markedly increased in the perinuclear cytoplasm and the dendrites. In the striatum the density of neurons exhibiting a sharp increase in immunoreactivity was more pronounced in the lateral than in the ventral part. In the hippocampus a strong reaction was present in all subfields but the CA1 subfield was particularly affected. The present study demonstrates for the first time that biosynthesis of a protein is markedly activated during the first 24 h of recirculation after 5-min cerebral ischemia of gerbils even in the vulnerable CA1 subfield, in which the overall protein synthesis is sharply reduced at the same time. Studying polyamine metabolism after ischemia may, thus, provide new information about the basic molecular mechanisms responsible for the altered gene expression after metabolic stress.
Of 491 patients operated for carcinomas of the colon or rectum between 1984 and 1989, 106 were tumour stage IV, U.I.C.C.(Dukes' 'D') at time of operation. In 22 of these cases a radical resection of the carcinoma of the colon or rectum and of synchronous liver metastases was performed simultaneously. In 20 patients the metastases were confined to one, in two they were found in both hepatic lobes. In one case a solitary metastasis of the lower lobe of the right lung was resected additionally. Three right-sided hemihepatectomies, one extended right hemihepatectomy, five left-sided hemihepatectomies, three left-sided lateral segmentectomies, seven atypical segmental resections and three wedge resections were performed. The mean operation time for the radical resection of the carcinomas of the colon or rectum as well as of the liver metastases was 3.5 (3-5.2)hours. An average of 3 (0-9) blood units were needed intraoperatively. The major liver resections were performed in complete normothermic vascular ischaemia using the finger fracture method. The time of ischaemia ranged between 8 and 25 min. Only 1 of 22 patients died postoperatively (30 days postoperative hospital mortality rate 4.5%). Five of 17 patients were free of tumour 2 years after operation. Eight of 22 were alive 2 years after operation (non-age corrected 2-year survival rate 36.4%), 2 of them are alive more than 5 years after treatment. Our results demonstrate that simultaneous resection of colon or rectum carcinoma and of synchronous (resectable) liver metastases can be performed successfully, even in a district hospital.
Cytochrome c oxidase of Paracoccus denitrificans is spectroscopically and functionally very similar to the mammalian enzyme. However, it has a very much simpler quaternary structure, consisting of only three subunits instead of the 13 of the bovine enzyme. The known primary structure of the Paracoccus denitrificans subunits, the knowledge of a large number of sequences from other species, and data on the controlled proteolytic digestion of the enzyme allow structural restrictions to be placed on the models describing the binding of the active metal centers to the polypeptide structure.
The extents of ATP-yielding and consuming processes in Ehrlich mouse ascites tumor cells during the proliferating and resting growth phase were compared. In the resting phase the total ATP production was decreased by one-third. The ATP supply by oxidative phosphorylation was drastically reduced, whereas the rate of glycolysis stayed nearly constant. All ATP-consuming processes investigated, i.e., protein turnover, Na+/K(+)-ATPase, Ca2(+)-ATPase, and RNA synthesis, were decreased proportionally with the total ATP consumption.
Trichomonas vaginalis homogenates were found to have an acid inorganic pyrophosphatase activity with a specific activity at pH 4.8 of about 7 nmol min-1 (mg protein)-1. This activity was localized predominantly in hydrolase containing particles, showed structure-bound latency and was tightly membrane-bound. The activity showed no magnesium dependence, a Km of about 2 mM inorganic pyrophosphate, a pH optimum of 5.2 and was inhibited by fluoride at millimolar levels. No evidence was obtained for the existence of a cytosolic magnesium-dependent activity but the existence of a low level of magnesium-independent cytosolic activity cannot be excluded. These observations correlate with the importance of cytosolic inorganic pyrophosphate in the carbohydrate catabolism in T. vaginalis.