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Biomedical subjects

G Sander

Publications and source records attributed to G Sander.

At least 37 records · Page 2Linked to original sources

A high-performance liquid chromatographic method for the determination of pseudouridine and uric acid in native human urine and ultrafiltered serum.

A simple and reliable HPLC method for quantitative determination of pseudouridine and uric acid in human urine and serum using a cation-exchange resin is described. This method is straightforward (12 runs of urine samples per day since the sample is only diluted into buffer and then chromatographed), sensitive, and highly reproducible. The column is stable over long periods (approximately 3 months of uninterrupted use at a time; it is thereafter easily restored to the original state). Mean excretion values for pseudouridine (in mumol/mmol creatinine) are 26.4 +/- 3.1 (17 female adults), 23.8 +/- 2.5 (12 male adults), 164.7 +/- 32.2 (37 male preterm infants); mean values for uric acid (mumol/mmol creatinine) are, respectively, 310.3 +/- 90.5, 278.2 +/- 56.1, and 1108 +/- 314. Human serum is deproteinized by pressure ultrafiltration in microcollodion bags with a nominal exclusion molecular weight of 12,400 and then put directly onto the HPLC column. The complete procedure takes 4 h.

Adult↗

[Herpes gestationis].

On the basis of two cases of herpes gestationis, the authors review this rare dermatosis which only occurs during pregnancy. In particular, they emphasise its auto-immune origin. Indirect immunofluorescence can be used to demonstrate the so-called herpes gestationis factor (HGF), a heat stable immunoglobulin G (IgG), in the maternal and foetal blood. The maternal prognosis is good and the cutaneous lesions respond well to treatment. The foetal prognosis is also good, however the transplacental transfer of the HGF is associated with a risk of foetal death and neonatal bullous dermatosis. In terms of aetiopathogenesis, the auto-immune HGF factor suggests a hypothesis of sensitisation to placental, foetal and/or paternal antigens under the influence of hormonal factors.

Adult↗

Quaternary opiate antagonists lower blood pressure and inhibit leucine-enkephalin responses.

The quaternary opiate antagonists naloxone methylbromide (MB) and naltrexone MB do not cross the blood-brain barrier, and may be used to differentiate peripheral from central nervous system effects of the opioid peptides. When administered intravenously to the conscious, chronically instrumented dog, naloxone MB transiently reduces mean systemic arterial pressure and increases heart rate in a dose-dependent manner over the concentration range from 0.1 to 1.0 mg/kg. The [Leu5]enkephalin response is completely inhibited at naloxone MB doses as low as 0.25 mg/kg, but this inhibition has terminated by 30 min after dosing. Naltrexone MB displays a similar spectrum of activity. This inhibition of the intravenous [Leu5]enkephalin response by the quaternary opiate antagonists indicates that the [Leu5]enkephalin response occurs by activation of peripheral receptor sites. The decrease in mean pressure induced by these antagonists coupled with the inhibition of the [Leu5]enkephalin response suggests that peripheral enkephalins may play a role in blood pressure regulation.

Animals↗

Ribosomal protein L1 from Escherichia coli. Its role in the binding of tRNA to the ribosome and in elongation factor g-dependent gtp hydrolysis.

Two Escherichia coli mutants lacking ribosomal protein L1, previously shown to display 40 to 60% reduced capacity for in vitro protein synthesis (Subramanian, A. R., and Dabbs, E. R. (1980) Eur. J. Biochem. 112, 425-430), have been used to study partial reactions of protein biosynthesis. Both the binding of N-acetyl-Phe-tRNA to ribosomes and the 6 to 8-fold stimulation of the elongation factor G (EF-G)-dependent GTPase reaction by mRNA plus tRNA, assayed in the presence of wild type 30 S subunits, were low with L1-deficient 50 S subunits. Addition of pure protein L1 to the assay restored both reactions to 100% of the control. By contrast, the basic EF-G GTPase reaction in the absence of mRNA and tRNA was not at all affected (mRNA alone had no effect). None of the following partial reactions were more than moderately modified by the lack of protein L1: binding to ribosomes of EF-G.GDP plus fusidic acid; the translocation reaction catalyzed by EF-G plus GTP; poly(U)-dependent binding to ribosomes of Phe-tRNAPhe (whether dependent on elongation factor Tu plus GTP or not); and the EF-Tu-dependent GTPase activity. It is concluded that protein L1 is involved in the interaction between ribosomes and peptidyl-tRNA (or tRNA) in the peptidyl site and consequently in the ribosomal GTPase activity depending on the simultaneous action of tRNA and EF-G.

Bacterial Proteins↗

Vitamin nutrition in patients on continuous ambulatory peritoneal dialysis (CAPD).

In 10 patients who had been on CAPD for 8.75 months, blood levels of the vitamins A, E, B-complex and C were measured and a precise diet history using food weighing for 3 days was obtained. Plasma vitamin A was elevated in all; since retinol binding protein (RPB) was elevated even more, the ratio of retinol to RBP was low. Vitamin E levels were also high. The vitamins B1, B2 and B6 were measured using erythrocyte enzyme activities. Vitamin B1 was low or borderline in 5, vitamin B6 was decreased in 3 and erythrocyte pyridoxal phosphate in 8 patients. Folic acid was low or borderline in 6 patients, whereas the vitamins B2 and B12 were normal in all. Vitamin C was diminished in 4 patients, and in dialyzate 60% of plasma concentrations were found. The intakes of the vitamins B1, B6 and B12 were below the recommended range. After supplementation of water soluble vitamins for 7 weeks the vitamins A and E remained elevated and B1 remained low, B6 and C had normalized in all and folic acid was markedly elevated. In CAPD decreased blood concentrations of some water soluble vitamins are found due to insufficient dietary intake and loss into dialyzate. Tentative recommendations are given for the replacement of the vitamins B1, B6, folic acid and C.

Adult↗

Leucine-enkephalin: reversal of intrinsic cardiovascular stimulation by pentobarbital.

In the conscious, chronically instrumented dog, leucine-enkephalin ([Leu5]ENK), 35 micrograms/kg injected intravenously, increased heart rate, respiratory rate, systolic and diastolic systemic arterial pressures, mean pulmonary arterial pressure, and cardiac output. After pentobarbital-induced anesthesia, the same dose of [Leu5]ENK decreased heart rate, systemic and pulmonary arterial pressures, and cardiac output. Responses both before and after pentobarbital were blocked by naloxone. These results indicate that barbiturate anesthesia can reverse the cardiovascular stimulatory activity of intravenously administered [Leu5]ENK.

Anesthesia↗

Properties and regulation of the GTPase activities of elongation factors Tu and G, and of initiation factor 2.

During protein synthesis the interaction with ribosomes of elongation factors Tu (EF-Tu), G (EF-G) and initiation factor 2 (IF-2) is associated with the hydrolysis of GTP which is directly related to the functions of the factors. In this article we review systematically the properties of these GTPase activities in the presence and absence of protein synthesis, and by examining the characteristics of the different minimal systems for the expression of these activities we point to the role of the various effectors and to the enzymological aspects of the systems. For EF-Tu, it has been possible to eliminate any requirement for macromolecular effectors, showing that the factor itself is a GTPase. For EF-G, the presence of at least the 50S ribosomal subunit has remained a requirement, whereas IF-2 needs both the 50S and 30S subunits to exhibit GTPase activity. Between the GTPase activities of the three factors there are some striking similarities, but important differences prevail as a consequence of the specificity of the different functions. This can also be seen by examining the respective ribosomal regions implicated in these reactions. When coupled with protein synthesis, the three GTPase activities reveal characteristics differing from those observed in partial systems.

Anti-Bacterial Agents↗

[Mechanism of action of the new antibiotic kirromycin].

The discovery and the elucidation of the mechanism of action of a new family of antibiotics is described. These antibiotics, here represented by kirromycin, all inhibit bacterial protein synthesis by acting on the protein elongation factor Tu, blocking its release from the ribosome during the elongation cycle and thereby inhibiting peptide bond formation. A number of these compounds have been successfully used as feed additives.

Animal Feed↗

Interaction of elongation factor Tu with the ribosome. A study using the antibiotic kirromycin.

Elongation factor Tu (EF-Tu) dependent GTP hydrolysis normally requires the presence of ribosomes and aminoacyl-tRNA (aa-tRNA). In the presence of the antibiotic kirromycin, the factor alone displays a GTPase activity that is enhanced by ribosomes and/or aa-tRNA [Wolf, H., Chinali, G., & Parmeggiani, A. (1974) Proc. Natl. Acad. Sci. U.S.A. 71, 4910-4914]. Using this system, we have found the following: (1) the 50S ribosomal subunit can substitute the 70S ribosome; (2) the 50S CsCl core a, b, and c particles [Sander, G., Marsh, R. C., Voigt, J., & Parmeggiani, A. (1975) Biochemistry 14, 1805-1814], lacking an increasing number of proteins, can induce ca. 65, 45, and 25%, respectively, of the EF-Tu-kirromycin GTPase activity of control 50S subunits, in the presence of 30S subunits and aa-tRNA; (3) addition of proteins L7/L12 with L10, but not of proteins L7/L12 free from L10, restored the activity of all the 50S CsCl cores in the EF-Tu-kirromycin-dependent GTPase to 70-90% of the control; (4) proteins L7/L12, with or without contaminating L10, did not induce any EF-Tu-dependent GTPase activity, in contrast to a recent report [Donner, D., Villems, R., Liljas, A., & Kurland, C. G. (1978) Proc. Natl. Acad. Sci. U.S.A. 75, 3192-3195], whether EF-Ts and/or kirromycin were present or not.

GTP Phosphohydrolase-Linked Elongation Factors↗

Phenytoin hypersensitivity presenting as postoperative fever.

One of the most catastrophic complications of intracranial surgery is infection. These infections present frequently as postoperative fever and a change in sensorium. Phenytoin is used frequently in conjunction with intracranial operation to prevent seizures. We report two patients in whom, although the full phenytoin sensitivity syndrome ultimately developed, the presenting sign was postoperative fever. The phenytoin sensitivity syndrome is reviewed with emphasis on the fact that all components of the syndrome are not always present initially. The clinical significance of the presentation of phenytoin hypersensitivity as postoperative fever is discussed.

Adult↗