Nuclear-encoded transfer RNAs in plant mitochondria.
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Amino Acids↗
Biomedical subjects
A Dietrich
Publications and source records attributed to A Dietrich.
[Routine gastroscopy before laparoscopic cholecystectomy: evaluation of the technology in 376 patients].
We performed endoscopy of the upper digestive tract in 376 patients before elective laparoscopic cholecystectomy. Abnormalities were found in 60 (15.9%); 14 patients had peptic ulcers, 15 gastric erosions, and 11 oesophagitis. Because of endoscopic findings 30 patients were treated medically and 2 by endoscopic polypectomy. Endoscopy lead us to cancel cholecystectomy in 4 patients; in 2 the complaints have persisted. Patients with abnormal endoscopic findings showed few significant differences in 40 variables (history and symptoms) compared with patients with normal findings. The incidence of ulcers, erosions or oesophagitis in patients over 72 years of age without loss of weight was 28.6%, compared with an overall incidence of 10.6%. Endoscopy confined to this group of patients, however, would have shown only 15% of all lesions. Consequently these predictors for endoscopic abnormalities had no practical benefit. Technology assessment according to the criteria of Fineberg et al. showed a health improvement for only 2 patients (0.5%). We conclude that routine endoscopy before laparoscopic cholecystectomy is not clinically useful in patients with symptomatic gallstone disease. This is exclusively related to patients with typical gallstone symptoms according to our definition.
Adolescent↗
Pharmacotherapy in shock syndromes: the neglected field of pharmacokinetics and pharmacodynamics.
Promising effects of adjuvant drugs in experimental shock models often are not confirmed in subsequent clinical trials, e.g., steroids, fibronectin, naloxone, immunotherapeutics. A key difficulty in establishing a therapeutic benefit in clinical studies, apart from study design shortcomings, is the lack of knowledge and application of principles of clinical pharmacokinetics and -dynamics. In shock states the relationship between an administered fixed dose regimen and the drug effect is strongly influenced by dynamic changes in absorption, distribution, metabolism, and elimination of the drug, all of which vary between individual patients. This article describes several neglected aspects of clinical pharmacology relevant to shock research under clinical conditions and discusses the indications, prerequisites, and limitations of "applied pharmacokinetics." The inclusion of therapeutic drug monitoring in clinical shock studies should be applied more frequently to establish experimental results in the "real world" of ICU settings.
Animals↗
Improving and maintaining preventive services. Part 1: Applying the patient path model.
Research in the past two decades has made remarkable progress in determining the variables that affect preventive care within primary care practices. The level of preventive care that a patient receives is largely determined by factors within the medical office setting. Many of these factors can be modified by physicians to encourage preventive care. An overview of these factors, presented as the Patient Path Model, can provide a framework for systematic practice evaluation. This model can be applied to almost any office setting to help identify opportunities to enhance and improve preventive care.
Humans↗
Improving and maintaining preventive services, Part 2: Practical principles for primary care.
Recent research has recognized several themes that have been common to many successful projects for increasing cancer screening and other prevention activities. The most common of these themes have been condensed into "principles for implementation," intended to help physicians and other health care providers to improve the provision of preventive medical care within their practices.
Humans↗
Physical map of human Xq27-qter: localizing the region of the fragile X mutation.
We describe a physical map of the end of the long arm of the human X chromosome encompassing the region from Xq27.2 to the q telomere, inclusive of the chromosomal band Xq28. This region is of particular interest, since it contains the highest density of genes associated with genetic diseases. The map covers a total of 12 megabases (Mb) of DNA and extends from the telomere to 3 Mb beyond the most likely position of the fragile X mutation, defined by a cluster of translocation breakpoints in somatic cell hybrids. The map determines order and position of loci throughout the Xq28 region and localizes cell line breakpoints marking the fragile X region to an interval of 300-700 kilobases between 8 and 8.7 Mb proximal of the Xq telomere.
Blotting, Southern↗
Molecular cloning and analysis of the fragile X region in man.
The fragile X syndrome (FraX), the most common inherited form of mental retardation, has been located to Xq27.3. As a step in the molecular analysis of this mutation, we have cloned a contiguous 1.8 Mb region containing the entire fragile X region in YAC and cosmid clones. The cloned area defines a region of 50 kb containing a CpG island, found to be selectively methylated in patients expressing the fragile X phenotype. In this 50kb area we have localised the breakpoints of four somatic cell hybrids selected to break at the position of the fragile site. Fluorescence in-situ hybridisation of cosmids flanking this area shows that the breakpoints, the CpG island and the fragile site coincide.
Chromosomes, Fungal↗
Conventional versus laparoscopic cholecystectomy and the randomized controlled trial. Cholecystectomy Study Group.
We considered using a randomized trial to assess the value of laparoscopic cholecystectomy in the treatment of symptomatic gallstones. The pros and cons for the timing of such a trial were in favour of not beginning the trial until surgeons learned to use the new procedure safely and effectively, and until key endpoints and outcome indices could be identified and assessed using valid measures. Instead an observational study was implemented to monitor the learning curve of surgeons as they mastered the laparoscopic equipment and procedures, and to assess the responses of the patients to the procedure. In the first 100 patients, the procedure proved to be as safe and feasible to use as conventional surgery, and there were strong benefits in terms of quicker recovery of the patients with less pain, discomfort, and a reduced length of hospital stay. The responses of the surgeons and the patients to the new procedure now place ethical constraints on the planning of a randomized controlled trial. Currently, comprehensive surveillance and monitoring of laparoscopic cholecystectomy is the only realistic method with which to assess the impact of this new technology in our clinic.
Adult↗
[Mediators and their antagonists in shock therapy].
The list of shock mediators currently comprises more than 150 candidates. A careful analysis using the criteria of Koch-Dale together with decision trees for exclusion of bias revealed that only histamine, C5a, beta-endorphin, tumor necrosis factor (TNF) thromboxane B2, platelet-activating factor (PAF), and oxygen free radicals are shown to be causally associated with shock symptoms. Although experimental studies with inhibitors of these mediators were convincing, there is still a lack of evidence under clinical conditions (exception histamine: anaphylactic shock). Combinations of antagonists against different causal mediators are the most promising future approaches.
Acute-Phase Proteins↗
Program for the visualization of inorganic crystals.
A program has been developed to manipulate images of inorganic structures and organic molecules on ALLIANT VFX/40 using the PHIGS + standard. This article reviews algorithms for representing spheres, ellipsoids and various polyhedrons involved in inorganic chemistry. The program also supports the display and manipulation of animated frames from dynamics simulations. Many graphical facilities have been implemented and we discuss their interest in the field of molecular graphics.
Algorithms↗
Syntheses of tolrestat analogues containing additional substituents in the ring and their evaluation as aldose reductase inhibitors. Identification of potent, orally active 2-fluoro derivatives.
A series of aldose reductase inhibitors were prepared which were analogues of the potent, orally active inhibitor tolrestat (1). These compounds (5, 7, 9, and 10) have an extra substituent on one of the unoccupied positions on the naphthalene ring of 1. Primary amide prodrugs of several members from the series 5 and 7, namely 6 and 8, respectively, were also prepared. These compounds were evaluated in two in vitro systems: an isolated enzyme preparation from bovine lens to assess their intrinsic inhibitory activity and an isolated sciatic nerve assay to determine their ability to penetrate membranes of nerve tissue. These compounds were also evaluated in vivo as inhibitors of galactitol accumulation in the lens, sciatic nerve, and diaphragm of galactose-fed rats. In general, compounds in series 5, 7, 9, and 10 were potent inhibitors of bovine lens aldose reductase. 2-Halo-substituted analogues from the series 5, 7, and 9 exhibited high activity in the nerve of the 4-day-galactose-fed rat, and in several instances, the primary amide prodrug 8 enhanced the in vivo potency of the respective carboxylic acid 7. Two 2-fluoro-derivatives, 8a and 9a, had especially high activity in vivo and were chosen for additional studies. These compounds were found to be approximately equipotent to tolrestat in the sciatic nerve of the galactose-fed rat and the STZ rat, as judged by their ED50's in these assays. Although primary amide analogue 8a did not have intrinsic inhibitory activity toward aldose reductase, it was metabolized to an active form in vivo and also in vitro within the sciatic nerve.
Administration, Oral↗
Fluorescent derivatives of bile salts. II. Suitability of NBD-amino derivatives of bile salts for the study of biological transport.
Interaction of unconjugated and taurine-conjugated NBD-amino-dihydroxy-5 beta-cholan-24-oic acids bearing the fluorophor in the 3 alpha, 3 beta, 7 alpha, 7 beta, 12 alpha, or 12 beta position with albumin results in a small hypsochromic shift of the emission maximum and an increase in quantum yield, suggesting binding by hydrophobic interactions. The different unconjugated fluorescent bile salt derivatives are metabolized by intact rat liver in different ways. The unconjugated 3 beta-NBD-amino derivative is completely transformed to its taurine conjugate and secreted as such, whereas the 3 alpha-NBD-amino derivative is completely transformed to a polar fluorescent compound not identical with its taurine conjugate. The unconjugated 7 alpha- and 7 beta-NBD-amino derivatives are only partially conjugated with taurine and mainly secreted in unmetabolized form. The unconjugated 12 alpha- and 12 beta-NBD-amino derivatives are not at all transformed to their taurine conjugates, but are partially metabolized to unidentified compounds. They are predominantly secreted as the unmetabolized compounds. In contrast to the unconjugated derivatives, all taurine-conjugated fluorescent bile salt derivatives are secreted into bile unmetabolized. With the exception of the 3 alpha-compound, all synthesized taurine-conjugated fluorescent derivatives interfere with the secretion of cholyltaurine. Differential photoaffinity labeling studies using (7,7-azo-3 alpha,12 alpha- dihydroxy-5 beta-cholan-24-oyl)-2'-[2'-3H(N)]aminoethanesulfonate as a photolabile derivative revealed that in liver cells all fluorescent bile salt derivatives interact with the same polypeptides as the physiological bile salts. The hepatobiliary transport of taurine-conjugated NBD-amino bile salt derivatives is, due to hydrophobic interactions, accompanied by an increase in fluorescence intensity which is favorable for the study of biological bile salt transport by fluorescence microscopy.
Albumins↗
[Glucocorticoids in multiple trauma and infection--still a topic for discussion?].
The clinical use of glucocorticoids in trauma and sepsis has not yet been approved on the basis of clinical trials. Current knowledge in the area of pathogenesis is reviewed, and against this background the mechanisms of steroid action will be discussed, the current status of clinical testing in both trauma and sepsis will be evaluated, and ways of testing the effectiveness will be proposed. Although most trials up to now have shown a positive overall effect in trauma patients, a further prospective randomized controlled study with a more homogeneous study population and including trauma scores is necessary before trauma can be reliably accepted as a firm indication for glucocorticoid treatment. In the discussion on sepsis syndrome a variety of reasons are suggested for the failure of earlier studies to show beneficial effects. Besides methodological aspects, one of the main reasons is the neglected field of pharmacologic-pharmacokinetic principles. A new study should be performed under therapeutic drug-monitoring (TDM) conditions once more is known about the target concentration range.
Animals↗
[Laparoscopic cholecystectomy. Initial experiences and results in 300 operations: a prospective follow-up study].
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Adolescent↗
A potato mitochondrial isoleucine tRNA is coded for by a mitochondrial gene possessing a methionine anticodon.
The nucleotide sequence of a potato mitochondrial tRNA(Ile) has been determined. This tRNA has a lysidine-like minor nucleotide in the first position of the anticodon (position 34). The corresponding mitochondrial gene has been cloned and sequenced. This gene has a CAT anticodon which corresponds to methionine. The C residue in the anticodon must therefore be post-transcriptionally modified. The mature tRNA has isoleucine-accepting activity but no methionine-accepting activity. This is the first report showing that in plant mitochondria a post-transcriptional modification could change the amino-acid specificity of a tRNA, as compared to that of the corresponding gene.
Anticodon↗
Transfer RNAs of potato (Solanum tuberosum) mitochondria have different genetic origins.
Total transfer RNAs were extracted from highly purified potato mitochondria. From quantitative measurements, the in vivo tRNA concentration in mitochondria was estimated to be in the range of 60 microM. Total potato mitochondrial tRNAs were fractionated by two-dimensional polyacrylamide gel electrophoresis. Thirty one individual tRNAs, which could read all sense codons, were identified by aminoacylation, sequencing or hybridization to specific oligonucleotides. The tRNA population that we have characterized comprises 15 typically mitochondrial, 5 'chloroplast-like' and 11 nuclear-encoded species. One tRNA(Ala), 2 tRNAs(Arg), 1 tRNA(Ile), 5 tRNAs(Leu) and 2 tRNAs(Thr) were shown to be coded for by nuclear DNA. A second, mitochondrial-encoded, tRNA(Ile) was also found. Five 'chloroplast-like' tRNAs, tRNA(Trp), tRNA(Asn), tRNA(His), tRNA(Ser)(GGA) and tRNA(Met)m, presumably transcribed from promiscuous chloroplast DNA sequences inserted in the mitochondrial genome, were identified, but, in contrast to wheat (1), potato mitochondria do not seem to contain 'chloroplast-like' tRNA(Cys) and tRNA(Phe). The two identified tRNAs(Val), as well as the tRNA(Gly), were found to be coded for by the mitochondrial genome, which again contrasts with the situation in wheat, where the mitochondrial genome apparently contains no tRNA(Val) or tRNA(Gly) gene (2).
Base Sequence↗
Structures of two isomeric hydroxamic acids: N-methyl-p-toluohydroxamic acid (MTH) and N-(4-methylphenyl)acetohydroxamic acid (MPA).
MTH, C9H11NO2, Mr = 165.19, monoclinic, P2(1)/n, a = 7.106 (2), b = 10.211 (3), c = 11.962 (2) A, beta = 97.99 (2) degrees, V = 859.5 A3, Z = 4, Dx = 1.276 Mg m-3, lambda(Mo K alpha) = 0.71069 A, mu = 0.054 mm-1, F(000) = 352, T = 138 K, final R = 0.042 for 1687 reflections with I greater than or equal to 2 sigma(I). MPA, C9H11NO2, Mr = 165.19, orthorhombic, Pbca, a = 9.300 (3), b = 9.463 (4), c = 19.340 (6) A, V = 1702.0 A3, Z = 8, Dx = 1.29 Mg m-3, lambda(Cu K alpha) = 1.5418 A, mu = 0.665 mm-1, F(000) = 704, T = 138 K, final R = 0.044 for 1362 reflections with I greater than or equal to 3 sigma(I). The hydroxamate group in each compound assumes the trans conformation as observed in other secondary hydroxamic acids. The interchange of the C and N substituents influences the planarity and dimensions (C = O, C-N bonds) of the hydroxamate moiety. In MTH the hydroxamate group shows significant deviation from planarity; the r.m.s. deviation of the four atoms, O = C-N-O(H), is 0.094 A, whereas in MPA it is only 0.004 A. This nonplanarity is due largely to out-of-plane bending at N, chi N = 23.9 (1) degree, as compared to chi N = 0.1 degree for MPA. The phenyl ring in MPA is nearly coplanar with the hydroxamate plane (dihedral angle of 10.3 degrees), but is significantly rotated from the hydroxamate plane in MTH (dihedral angle of 43.8 degrees). Electronic differences in the two molecules are considered.
Benzeneacetamides↗
Solution conformation of several free tRNALeu species from bean, yeast and Escherichia coli and interaction of these tRNAs with bean cytoplasmic Leucyl-tRNA synthetase. A phosphate alkylation study with ethylnitrosourea.
The solution conformation of eight leucine tRNAs from Phaseolus vulgaris, baker's yeast and Escherichia coli, characterized by long variable regions, and the interaction of four of them with bean cytoplasmic leucyl-tRNA synthetase were studied by phosphate mapping with ethylnitrosourea. Phosphate reactivities in the variable regions agree with the existence of RNA helices closed by miniloops. At the junction of these regions with the T-stem, phosphate 48 is strongly protected, in contrast to small variable region tRNAs where P49 is protected. The constant protection of P22 is another characteristics of leucine tRNAs. Conformational differences between leucine isoacceptors concern the anticodon region, the D-arm and the variable region. In several parts of free tRNALeu species, e.g. in the T-loop, phosphate reactivities are similar to those found in tRNAs of other specificities, indicating conformational similarities among tRNAs. Phosphate alkylation of four leucine tRNAs complexed to leucyl-tRNA synthetase indicates that the 3'-side of the anticodon stem, the D-stem and the hinge region between the anticodon and D-stems are in contact with the plant enzyme.
Alkylation↗