Biomedical subjects
Publications and source records attributed to B Hess.
6-Phosphofructo-2-kinase (PFK2) is activated by a cAMP-dependent protein kinase, and inactivated by phosphatase, indicating the interconversion of PFK2. Inorganic phosphate also activates PFK2, and the optimum pH for the PFK2 activity varies with the concentration of phosphate. Phosphate also enhances the inactivation of PFK2 by citrate, suggesting that phosphate acts as a regulator of PFK2.
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The numerical analysis for a glycolytic model containing the enzymes phosphofructokinase and pyruvate kinase reveals different types of entrainment, as well as chaotic response under sinusoidal substrate input. Entrainment with response periods 1, 2, 3, 5 and 7-times the input flux period and aperiodic behaviour is verified by measurements of NADH fluorescence in extracts of Saccharomyces cerevisiae in the theoretically predicted range. The stroboscopic transfer function obtained from the aperiodic signal admits period 3, implying chaos according to the Li-Yorke theorem.
A high-performance liquid chromatographic assay has been developed for the imidazo quinazoline derivative Ro 13-6438 [D-(-)-6-chloro-1,5-dihydro-3-methylimidazo(2,1-b)-quinazolin++ +-2(3H)-one], which is under clinical investigation as a cardioactive drug. The drug is extracted from biological fluids into 1-chlorobutane--1-hexanol (90:10) and back-extracted into perchloric acid. This extract is chromatographed directly, using a reversed-phase high-performance liquid chromatographic system with ultraviolet detection at 254 nm. The detection limit in plasma is about 1 ng ml-1, using a 1-ml sample. The assay is rapid, accurate and sufficiently sensitive for the study of the single-dose kinetics of Ro 13-6438 in man following a 7.5-mg intravenous dose. No instability of the unchanged substance was observed in plasma during storage for one day at room temperature and for five months at --20 degrees C.
The pharmacokinetics of phenytoin are studied in 2 patients on CAPD treatment. Free and protein bound phenytoin are lost in the dialysate. The peritoneal clearance of phenytoin varies from 1.6 to 2.4 ml/min. The peritoneal mass transfer varies from 0.022 to 0.059 mumol/min, depending on the phenytoin dose given. The dialysate concentrations of phenytoin reach 40% of the serum levels. Peritoneal losses of phenytoin may be 5% of the daily intake. The clinical significance of serum level measurements in monitoring of phenytoin therapy is discussed. Beside clinical symptoms, the serum free phenytoin level is of most importance. In uremic patients the albumin-bound fraction of phenytoin is reduced.
A glycolytic model system consisting of the enzymes phosphofructokinase (EC 2.7.1.11) and pyruvate kinase (EC 2.7.1.40) is analyzed when subject to periodic substrate addition. The calculations are performed by using detailed rate laws that have been derived for the enzymes of Escherichia coli. Due to linear relationships between the metabolite concentrations, the numerical solutions can be displayed inside a trapezium, so that the concentrations of four different metabolites are indicated along the trapezium edges. The analysis reveals a rich variety of time patterns, corresponding to different periodic, quasiperiodic, and chaotic attractors. These patterns undergo complex hysteresis loops when bifurcation parameters are slowly changed-for example, by modulating the input amplitude. By using this technique up to four attractors coexisting in phase space are found. The time patterns corresponding to coexisting attractors can be switched into one another by triggering the system with short substrate pulses. Furthermore, conditions exist at which the triggering is autonomous-i.e., self-sustained (intermittent) switchings occur. The time between these switchings can be set externally by the value of the input amplitude. For conditions in which the periods of the oscillations are in the order of minutes, the self-sustained switching-which modulates these oscillations-can be in the order of hours.
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Rat adrenocortical cells take up high density lipoprotein cholesterol for use as steroidogenic substrate. To better understand this unique uptake process, we have first characterized HDL binding. Infusion of human 125I-labeled HDL into rats pretreated with 4-APP demonstrated that the adrenal and ovary accumulate HDL in a saturable fashion in vivo. Subsequent studies using isolated rat adrenocortical cells demonstrated that cellular uptake of HDL is comprised of two events. One event is characterized by reversible membrane binding and is complete by 60 min (t1/2 = 20 min). The second event is marked by irreversible apoprotein accumulation which continues for at least 3 hr. Reversibly bound material exhibits the same apoprotein distribution as unincubated HDL. Irreversible accumulation could not be attributed to internalization or lysosomal accumulation inasmuch as it also occurred with partially purified plasma membranes and was not enhanced by addition of chloroquine. Reversible binding of human HDL3 exhibited a saturable dependence on concentration (Kd = 27 micrograms protein/ml; N = 3.0 X 10(6) sites/cell) similar to that previously reported for rat liver, ovary, and testis. Cell accumulation of HDL decreased by over 80% at 4 degrees C compared to 37 degrees C, did not require calcium, and was not diminished by prior cell treatment with trypsin or pronase. These results indicate that rat adrenocortical cells possess plasma membrane recognition sites for HDL with different properties than those of the LDL receptor. Moreover, adrenal accumulation of HDL apoproteins does not lead to secondary lysosome formation.
The influence of fructose 1,6-bisphosphate and Ca2+ on the kinetics of pyruvate kinase from Escherichia coli K12 was studied (at pH 7.0 and 25 degrees C) by using the pH-stat method for the measurement of the reaction progress as well as initial-rate analysis. The data were analysed on the basis of a concerted model with three conformational states [Markus, Plesser, Boiteux, Hess & Malcovati (1980) Biochem. J. 189, 421-433] by using a novel procedure for a computer-directed treatment of progress curves [Markus & Plesser (1976) Biochem. Soc. Trans. 4, 361-364]. By addition of fructose 1,6-bisphosphate the sigmoid kinetics with respect to phosphoenolpyruvate and Mg2+ is abolished and the activity of the enzyme is described by classical saturation kinetics. This is explained by exclusive binding of fructose 1,6-bisphosphate at an allosteric site of the conformational state that forms the active complex. We observe that Ca2+ is an activator of the enzyme at low Mg2+ and Ca2+ concentrations; otherwise it is an inhibitor. These effects can be understood by assuming that Ca2+ has the same binding properties as Mg2+, although it does not allow a catalytic turnover.
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Case report on a 48-year-old Swiss male living in Burundi who suddenly fell ill with vomiting and anorexia, followed by pappy stools, weakness and impotence. He presented with hepatomegaly, while sedimentation rate and alkaline phosphatase were both elevated. Stool examination revealed cysts and vegetative forms of Entamoeba histolytica, while amebic serology was negative. Treatment with ornidazole and later with diloxanide furoate was given. Sonography showed two cystoid areas in the right lobe of the liver. In the third sonographically guided fine-needle puncture both lesions were fully aspirated. Amebic serological tests were now positive for the first time. Six weeks later the sonogram showed a normal liver feature. The symptomatology and diagnosis of hepatic amebic abscess are discussed, with special reference to the important role of sonographically guided fine-needle puncture and drainage. Sonographic technique and differential diagnosis are briefly demonstrated.
A 53-year-old, previously healthy man developed persistent diarrhea 4 days after ingestion of smoked but uncooked pork sausages in the Southern Tyrol. On his return to Switzerland he ate the same sausages and was admitted to hospital with migrating muscle pain, fever and chills. While fever and diarrhea soon regressed, the patient exhibited neurologic symptoms and change of character. The leukocyte count was 14 000/mm3 with 39% eosinophils. 40 days after hospitalization a second muscle biopsy established the diagnosis of Trichinella spiralis infection. At the same time, serologic tests were positive for Trichinella spiralis. Epidemiology, parasitology, symptomatology, diagnosis, therapy, prophylaxis and prognosis of trichinellosis are briefly discussed.
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"Spontaneous" rupture of the oesophagus is rare and happens after a marked rapid rise in intraluminal oesophageal pressure (massive vomiting, asthma etc.). As is known from the literature, forceful swallowing alone may produce spontaneous perforation in the case of damage to the mucosa or muscular layer of the oesophagus. Boerhaave's syndrome associated with rare diffuse idiopathic muscular hypertrophy of the lower oesophagus has been described in only three cases in the literature.
The ratio of protons released per M-412 intermediate formed in illuminated purple membrane sheets of Halobacterium halobium varies from 0.3 to 3.0 as a function of the ionic strength and light intensity. The ratio increases with decreasing light intensity. At high ionic strength the illumination time affects the monophasic rate of proton uptake and biphasic rates of the M-412 decay. The influence of the ionic strength on the ratio is discussed on the basis of Gouy-Chapman theory as a consequence of pKa shifts of light-activated proton binding groups.
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The design of the glycolytic pathway resulting from the continuous refinement of evolution is discussed with regard to three aspects. 1. Functional and structural properties of individual enzymes. The catalytic constants of the glycolytic enzymes are remarkably optimized; the turnover numbers are within one order of magnitude. The same is true for the molarities of catalytic centres in the cytosol, as is noted for yeast. Functional properties of the enzymes are reflected in their tertiary and quaternary structures. 2. Regulatory mechanisms of single enzymes. A classification of the various types of enzymic control mechanisms operating in the glycolytic pathway is given. In addition to the usual Michaelis-Menten saturation kinetics and the various types of inhibition there is control by positive and negative effectors based on oligomeric structures (fast acting, fine control) as well as regulation by chemical interconversion structures (fast acting, fine control) as well as regulation by chemical based on enzymes cascades (slow acting, very effective). 3. Functional and regulatory mechanisms of the whole glycolytic reaction pathway. A prominent feature is the high enzyme:substrate ratio, which guarantees fast response times. However, a quantitative treatment of the overall kinetics is limited by an incomplete knowledge of the enzymes' dynamic and chemical compartmentation as well as some of their control properties. From an analysis of the oscillatory state, certain control points in the glycolytic chain can be located that coincide with major branching points to other metabolic pathways. These points are controlled by fast-acting cooperative enzymes that operate in a flip-flop mechanism together with the respective antagonistic enzymes, preventing futile cycles. The gating enzymes leading to the glycogen store and the citric acid cycle are of the slow-acting but very effective interconvertible type. The combination of all the complex and intricate features of design yields a glycolytic network that enables the cell to respond to its various metabolic needs quickly, effectively and economically.
In common with the F1-ATPase from other sources, yeast mitochondrial F1-ATPase was inhibited by 4-chloro-7-nitrobenzofurazan. Total inhibition of the F1-ATPase activity was compatible with the modification of a single tyrosine residue per F1-ATPase molecule. Radioactive labelling experiments localized this modification on a beta-subunit. The inactive modified enzyme retained the capacity to bind the photoaffinity label 8-azido-1,N6-etheno-ATP, which has previously been shown to bind nucleotide sites of low affinity. As well, the inactive modified enzyme bound MgATP with high affinity, yielding a Kd of 14 microM. The results are consistent with the hypothesis of alternating, or cooperative, site catalysis by F1-ATPase.