Subject(s)
Bacteriology/history , Eponyms , Germany , History, 19th Century , History, 20th Century , Mycology/historySubject(s)
Foot/innervation , Peroneal Nerve/injuries , Aged , Humans , Knee Injuries/complications , Male , PrognosisSubject(s)
Child Welfare/history , Famous Persons , Literature, Modern/history , Orphanages/history , Child , History, 19th Century , Hospitals, Pediatric/history , Humans , London , PovertySubject(s)
Medicine , Social Welfare/history , History, 18th Century , Religion and Medicine , Science/history , United KingdomABSTRACT
An unusual effect of badly fitting swimming goggles is described. The goggles pressed on the trochlea of the left eye, interfering with the action of the superior oblique muscle. Diplopia resulted, which took several weeks to resolve.
Subject(s)
Diplopia/etiology , Eye Protective Devices/adverse effects , Swimming , Humans , Male , Oculomotor Muscles/injuriesABSTRACT
Understanding the natural variability of climate is important for predicting its near-term evolution. Models of the oceans' thermohaline and wind-driven circulation show low-frequency oscillations. Long instrumental records can help validate the oscillatory behavior of these models. Singular spectrum analysis applied to the 335-year-long central England temperature (CET) record has identified climate oscillations with interannual (7- to 8-year) and interdecadal (15- and 25-year) periods, probably related to the North Atlantic's wind-driven and thermohaline circulation, respectively. Statistical prediction of oscillatory variability shows CETs decreasing toward the end of this decade and rising again into the middle of the next.
Subject(s)
Antivenins/therapeutic use , Scorpion Stings/etiology , Scorpion Venoms/poisoning , Animals , Child, Preschool , Humans , ScorpionsABSTRACT
The present results suggest that the enzyme modifier citrate and the substrate isocitrate are bound at different sites on yeast NAD-specific isocitrate dehydrogenase and that citrate diminishes the binding of the positive effector 5'-AMP, thereby causing a decreased rate of enzyme catalysis. This interpretation differs from the earlier proposal that citrate can replace isocitrate at an activator site on the enzyme and can cause inhibition by binding at its catalytic site [Atkinson et al. (1965) J. Biol. Chem. 240, 2682]. The present proposal is supported by the following observations: At constant subsaturating levels of isocitrate, NAD+, and Mg2+ without AMP, up to 10 mM citrate was an activator and not an inhibitor. Citrate decreased velocity for AMP-activated enzyme; however, with increasing citrate the specific activity with AMP asymptotically approached but did not decrease below the level of the enzyme maximally activated by citrate in the absence of AMP. When added singly, AMP decreased S0.5 for isocitrate without changing the Hill number (n), whereas citrate lowered n without changing S0.5 for isocitrate. The difference in action of these modifiers indicated that they were bound at separate sites on the enzyme. The binding of citrate appeared to cause a conformational change in the protein that lowered the enzyme's affinity for AMP. This was consistent with the findings that citrate (or the citrate agonist fluorocitrate) (i) resulted in an increase in S0.5 for isocitrate with the AMP-activated enzyme and (ii) decreased binding of the positive effector analogue TNP-AMP as measured by fluorescence change.(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
Citrates/pharmacology , Isocitrate Dehydrogenase/metabolism , NAD/metabolism , Yeasts/enzymology , Adenosine Monophosphate/metabolism , Catalysis , Citric Acid , Enzyme Activation , Isocitrate Dehydrogenase/antagonists & inhibitors , Kinetics , Magnesium/metabolism , Spectrometry, FluorescenceABSTRACT
The specificity of yeast NAD-specific isocitrate dehydrogenase for the structures of the allosteric effector 5'-AMP was examined with analogues modified in the purine ring, pentosyl group, and 5'-phosphate group. An unsubstituted 6-amino group was essential for activation as was the phosphoryl group at the 5'-position. Activity was retained when an oxygen function of the 5'-phosphoryl was replaced by sulfur (Murry & Atkinson, 1968) or by nitrogen (phosphoramidates). 2-NH2-AMP, 2-azido-AMP, and 8-NH2-AMP were active; 8-azido-AMP and 8-Br-AMP were inactive. The configuration or nature of substituents about carbons 2' and 3' of the pentosyl portion of AMP was not critical for allosteric activation since AMP analogues containing, e.g., 2',3'-dideoxyribose or the bulky 2',3'-O-(2,4,6-trinitrocyclo-hexadienylidene) substituent (TNP-AMP) were active. TNP-AMP was bound to the enzyme with fluorescence enhancement and had an S0.5 for activation similar to the S0.5 for AMP. Positive effector activity was decreased when the pentosyl moiety of 5'-AMP was replaced by the six-membered nitrogen-containing morpholine group, indicating that the pentosyl group may be critical as a spacer for the proper geometry of binding to enzyme at the 6-amino and 5'-phosphoryl groups of 5'-AMP. A comparison of molecular models of 5'-AMP with 8,5'-cycloAMP suggests that the species of 5'-AMP required for binding to the enzyme contains the purine and ribose moieties in an anti conformation and positioning of the 5'-phosphate trans with respect to carbon 4'.(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/metabolism , Isocitrate Dehydrogenase/metabolism , NAD/metabolism , Saccharomyces cerevisiae/enzymology , Adenosine Monophosphate/pharmacology , Allosteric Regulation , Allosteric Site , Chromatography , Chromatography, Gel , Durapatite , Hydroxyapatites , Isocitrate Dehydrogenase/isolation & purification , Kinetics , Ligands , Molecular Structure , NAD/isolation & purification , Spectrometry, Fluorescence , Structure-Activity RelationshipABSTRACT
Together with a general assessment of gerontopsychiatric care in the Federal Republic of Germany, the paper presents a model in hospitalised gerontopsychiatric treatment that has been tested at Hanover College of Medical Studies (Medizinische Hochschule Hanover). Results presented cover a wide range of divergent disorders, and appear to justify the employment of the model elsewhere.