Nature of quantum chaos in spin systems.
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Biomedical subjects
Publications and source records attributed to G Müller.
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Iron uptake by Escherichia coli under aerobic conditions of iron deficiency is mediated by a highly stable ferric enterobactin [Fe(ent)3-] siderophore complex. Mössbauer spectroscopy has been used to monitor the fate of the iron as 57Fe(ent) was taken up by the cells. Osmotic shock experiments were used to distinguish between the iron present in the periplasmic space and that in the cytoplasm of the cell. Iron delivery by a synthetic analog of enterobactin, 1,3,5-N,N',N''- tris-(2,3-dihydroxybenzoyl)triaminomethylbenzene (MECAM), was also studied. Although Fe-MECAM was transported at the same rate as was Fe(ent) across the outer membrane and was apparently accumulated in the periplasmic space, the subsequent behaviors of Fe(ent) and Fe-MECAM were very different. After more than 30 min, a major fraction of the iron originally absorbed as ferric enterobactin appeared as Fe(II), apparently in the cytoplasm of the cell. However, little iron was delivered to the cytoplasm by the MECAM complex. The differences in specificity of these two stages of iron uptake by E. coli are discussed.
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The skeletal influence on muscle development was investigated taking an experimental and comparative approach. Chick hindlimbs of HH stage 23 were operated in order to induce the development of an enlarged, elongated fibula - similar to the condition in bird ancestors. The skeletal change resulted in a series of secondary alterations in the later-forming zeugopod muscles. By comparing the results to the zeugopod musculature in other birds and in reptiles it could be shown that changes did not occur at random but resembled the patterns of interspecific variation and ancestral arrangement. It is concluded that skeletal elements influence muscle morphogenesis during a certain period of development. A classification of four phases in muscle development is presented: formation of the premuscular masses; individuation of separate muscles; final shaping and insertion; development maintenance and growth. The factors acting on each level are discussed and it is suggested that skeletal influence becomes effective in phase 3. The results also emphasize the role of development in evolution. The experimental reestablishment of an ancestral epigenetic condition within a developing organ system resulted in ancestral features of subsequently forming characters. This suggests that modification of epigenetic control of gene expression may be an important mechanism in evolutionary change.
Model experiments with mice are presented in which the defense against challenge infections has been checked after immunization with various living and killed vaccines of Pasteurella. A temperature sensitive Pasteurella mutant has proved to be superior to inactivated bacteria. It has been established that different routes of administration result in different effects. In this context, intraperitoneal, intramuscular and intratracheal administration have resulted in the highest protection rates, even when combined with oral and aerogeneous immunizations, which are of little efficacy when used exclusively. The importance of a change in the route of administration during repeated immunizations is discussed.
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Prostanoids are important for the pathogenesis of chronic inflammatory bowel diseases as mediators of inflammatory, immune and allergic reactions. The levels of thromboxane B2(TXB2), the stable hydrolysis product of thromboxane A2(TXA2) were determined in blood plasma of patients with chronic inflammatory bowel diseases. The platelet malondialdehyde (MDA) formation was determined as an indicator of the TXA2 synthetase activity. The TXB2 concentrations were measured radioimmunologically. The platelet MDA formation induced by N-ethylmaleimide was investigated with the thiobarbituric acid reaction. The investigated patients (n = 10) suffering from ulcerative colitis had a significant increasing (p less than 0.02) of the platelet MDA formation (mean = 4.39 nmol/10(9) platelets) in comparison to the normal group (n = 20; mean = 2.87; nmol/10(9) platelets). The increasing of TXB2 levels was not significantly different than in normal control subjects. The plasma concentrations of 6-keto-PGF1 were situated on the limit of detection.
Increased oxalic acid absorption, hyperoxaluria and oxalatelithiasis are found in many gastroenterological diseases. All persons receive 370 kBq 14C-oxalic acid for the measurement of oxalic acid absorption. The absorbed and in the urine excreted 14C-activities are measured with a scintillation spectrophotometer and scintillator composed of 2,5-diphenyloxazole(POP), 1,4-bis-(4-methyl-5-phenyl-2-oxazolyl)benzene (dimethyl-POPOP), naphthalene, toluene and ethyleneglycol monomethylether. Normal values of oxalic acid absorption are means +/- S = 7.17 +/- 1.87%/24 h (n = 40).
In view of the benign clinical course of the atypical adenoma and the high diagnostic accuracy of our frozen sections we feel that subtotal strumectomy with in toto removal of the adenoma and closely spaced follow-ups constitutes an adequate treatment of this thyroid neoplasm. In our opinion primary lobectomy means unnecessarily exposing a disproportionately high percentage of patients to the higher complication risk of this more radical surgery. From 1977 to 1982 there were 47 cases of atypical adenoma among our patients. The ratio men: women was 1:3.7, the mean age of the patients was 44 years. The patients underwent subtotal strumectomy. In the period under review "atypical adenoma" diagnosed on the basis of frozen sections turned out to be carcinoma in 5 instances. The follow-up period of the 47 patients that underwent surgery ranges from 1 1/2 to 7 years. None of the patients has had tumor regrowth so far.
Cultured cells of the higher plant Corydalis sempervirens Pers. which had been adapted to growing in the presence of 5 mM glyphosate (N-[phosphonomethyl]-glycine), a herbicide and a potent specific inhibitor of the shikimate pathway enzyme 5-enol-pyruvylshikimate-3-phosphate (EPSP) synthase, had a nearly 40-fold increased level of the extractable activity of EPSP synthase. Activities of five other shikimate pathway enzymes were, however, similar in the adapted and nonadapted cells, and the concentrations of the free aromatic amino acids in the two cell lines were also similar. EPSP synthases purified from glyphosate-adapted, as well as nonadapted cells, had identical physical, kinetic, and immunological properties, which indicated that the glyphosate-sensitive enzyme was overproduced in the adapted culture. Overproduction of EPSP synthase in the adapted culture was unequivocally established by two-dimensional polyacrylamide gel electrophoresis, as well as by one-dimensional sodium dodecyl sulfate-gradient gel electrophoresis and quantitation of EPSP protein by immunoassay after transfer to nitrocellulose membranes. While about 0.06% of the total soluble protein from nonadapted cells was EPSP synthase protein, the proportion was 2.6% in the adapted cells. In vivo pulse-labeling experiments with [35S]methionine established that the adapted cells have an increased rate of EPSP synthase protein synthesis.
The yeast Rhodotorula pilimanae produces the dihydroxamate siderophore rhodotorulic acid (RA) in prodigious amounts when starved for iron. Synthetic dihydroxamate analogs of RA have been prepared in which the diketopiperazine ring of RA is replaced by a simple chain of n methylene groups. It is found that R. pilimanae is able to accumulate iron using these achiral complexes, as well as from simple monohydroxamate analogs, at rates comparable to those of RA. While the Fe2RA3 complex does not enter the cell, there is a receptor system whose geometric requirements for siderophore recognition have been probed using analogs. In contrast to mono- or dihydroxamate ligands, the trihydroxamate siderophores such as ferrioxamine B are completely ineffective at delivering iron to R. pilimanae. This is ascribed to the greater stability of these complexes, which blocks release of the Fe(III) in a ligand exchange process that is required for uptake. To explore whether this ligand exchange involves redox catalysis, Ga(III) was substituted for Fe(III). The gallium was taken up at rates near those of iron and were also energy-dependent, as determined by metabolic inhibition with KCN.
Rhodotorulic acid (RA), a dihydroxamate siderophore produced by Rhodotorula pilimanae, forms 3:2 complexes with ferric and chromic ions (M2RA3) at pH 7. Kinetically inert chromic complexes of RA have been separated into geometrical isomers and for the first time partially resolved into optical isomers. The three isomers delta-cis, delta-trans, and lambda-trans were characterized by their visible and circular dichroism spectra. Inhibition by both delta-isomers of radiolabeled ferric RA uptake in R. pilimanae was equally effective. However the lambda-cis isomer was significantly less effective as an inhibitor. Concentration-dependent uptake kinetics were performed with ferric RA and the ferric complex of synthetic enantio-RA, which form predominantly delta and lambda complexes, respectively. The lambda-enantio-Fe2RA3 was 50% less effective in supplying iron to R. pilimanae than was Fe2RA3. An additional synthetic analog of RA, which lacks a carbonyl group at the diketopiperazine ring, exhibited the same uptake rates as ferric RA. We conclude that stereoselective recognition of optical isomers takes place during iron uptake mediated by RA and that this recognition primarily involves the right-handed delta coordination "propellor" of the metal center and its adjacent functionalities.
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The tyrosine aminotransferase (TAT) gene is expressed in a tissue and developmental-specific manner. In addition, this gene is regulated by glucocorticoid and polypeptide hormones and its expression is affected when a regulatory region near the albino locus of the mouse is deleted. In order to allow studies of the molecular effects of these deletion mutations we have isolated and characterized the mouse TAT gene. The gene is 9.2 x 10(3) bases in length and consists of 12 exons which give rise to a 2.3 x 10(3) base long messenger RNA. The DNA sequence at the 5' end of the gene was determined and compared with the corresponding sequence of the rat tyrosine aminotransferase gene. The sequence comparison showed extensive homology over the entire region sequenced. In addition, DNA: DNA heteroduplex studies between the mouse and rat tyrosine aminotransferase genes revealed that this homology extends over the entire gene and its flanking sequences. The mouse tyrosine aminotransferase gene has been mapped distal to the serum esterase-1 locus on mouse chromosome 8, using a restriction fragment length polymorphism between two mouse species. Since the albino deletions are located on mouse chromosome 7, the assignment of the TAT gene to chromosome 8 suggests that a regulatory factor(s) affecting TAT gene expression acts in trans.
Coronavirus-like particles were identified by electronmicroscopy in the feces of homosexual men. The particles banded at a density of 1.21 g/ml after cesium chloride density gradient centrifugation. To determine whether the presence of this virus might be related to clinical symptoms, several patient groups were studied prospectively. In 8 of 16 (50%) homosexual males with acquired immunodeficiency syndrome (AIDS) or unexplained lymphadenopathy syndrome (LAS), coronavirus particles were found. In contrast, such particles were found in none of 18 heterosexual controls and in only 3 of 20 homosexual males without AIDS or LAS. Thus, coronavirus excretion correlated significantly (2 alpha less than 0.01) with the clinical diagnosis of AIDS or with syndromes belonging to the AIDS-related complex. In addition, such particles identified in the serum of one patient with LAS and diarrhea suggest invasion and systemic spread of the agent and underline that this virus behaves differently from "common cold" human coronaviruses.
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