[Sinus histiocytosis with cutaneous lesions and thoracic herpes zoster].
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Adult↗
Biomedical subjects
M Gilbert
Publications and source records attributed to M Gilbert.
Saccharomyces cerevisiae SSB1 protein and its relationship to nucleolar RNA-binding proteins.
To better define the function of Saccharomyces cerevisiae SSB1, an abundant single-stranded nucleic acid-binding protein, we determined the nucleotide sequence of the SSB1 gene and compared it with those of other proteins of known function. The amino acid sequence contains 293 amino acid residues and has an Mr of 32,853. There are several stretches of sequence characteristic of other eucaryotic single-stranded nucleic acid-binding proteins. At the amino terminus, residues 39 to 54 are highly homologous to a peptide in calf thymus UP1 and UP2 and a human heterogeneous nuclear ribonucleoprotein. Residues 125 to 162 constitute a fivefold tandem repeat of the sequence RGGFRG, the composition of which suggests a nucleic acid-binding site. Near the C terminus, residues 233 to 245 are homologous to several RNA-binding proteins. Of 18 C-terminal residues, 10 are acidic, a characteristic of the procaryotic single-stranded DNA-binding proteins and eucaryotic DNA- and RNA-binding proteins. In addition, examination of the subcellular distribution of SSB1 by immunofluorescence microscopy indicated that SSB1 is a nuclear protein, predominantly located in the nucleolus. Sequence homologies and the nucleolar localization make it likely that SSB1 functions in RNA metabolism in vivo, although an additional role in DNA metabolism cannot be excluded.
Amino Acid Sequence↗
Pregnancy-induced insulin resistance in liver and skeletal muscles of the conscious rabbit.
Insulin sensitivity of maternal nonuterine tissues (liver and skeletal muscles) has been investigated in the conscious rabbit during late gestation (24 and 30 days). The specific effect of insulin on glucose production and utilization was evaluated with the hyperinsulinemic euglycemic clamp technique. The net balance of glucose across the hindlimb muscles was studied by means of the Fick principle in basal and insulin stimulated conditions (clamp study). Our results show that an insulin-resistant state develops between days 24 and 30 of gestation in the rabbit and involves both glucose producing (liver) and utilizing (muscles) tissues. On day 30 of gestation, muscle glucose uptake was not significantly stimulated at a plasma insulin concentration of 700 microU/ml, whereas it was stimulated by 30-40% in nonpregnant and 24 day pregnant rabbits. At similar plasma insulin concentration, endogenous glucose production was suppressed by 85% in both nonpregnant and 24 day pregnant rabbits, whereas it was decreased by only 30% in 30 day pregnant rabbits. The present data suggest that hindlimb muscles of late pregnant rabbits are able to reduce their insulin-induced glucose utilization. This could contribute to meet the glucose requirements of pregnant uterus in late gestation.
Animals↗
Studies of gut and hepatic metabolism in conscious rabbits.
The present study was designed to develop the techniques for chronic catheterization of the hepatic and portal venous circulation in conscious rabbits and to apply these techniques to a study of hepatic metabolism in this species. Experiments were made after an 18-h fast and for 4 h after the initial feeding. Measurements of arteriovenous differences of substrates were combined with measurements of hepatic and gastrointestinal blood flow. Hepatic glucose production was suppressed by 60% at 1 h and had returned to control levels by 4 h. The hepatic uptake of lactate declined slightly at 1 h and had returned to control level 2 h after the meal. There was a marked and rapid fall in hepatic ketone body output after refeeding. Although amino acid concentrations displayed a transient increase 1 h after the meal, only the arterial concentration of branched-chain amino acids remained significantly elevated for 4 h. The total hepatic uptake of the gluconeogenic amino acids (alanine, serine, threonine) remained constant. Refeeding resulted in a doubling of arterial insulin concentrations at 1 h followed by a progressive decline over the next 3 h. It is concluded that in rabbits fed a mixed meal partial suppression of hepatic glucose output is mainly due to a decline in glycogenolysis rather than a decrease in gluconeogenesis, shortly after refeeding the liver is able to virtually shut off its ketone body production, the major gluconeogenic precursors (lactate, alanine, glycine, serine, and threonine) may contribute to approximately 40% of the glucose release.(ABSTRACT TRUNCATED AT 250 WORDS)
Amino Acids↗
Development of enzymes of glycerol metabolism in human fetal liver.
The activities of three key enzymes of glycerol metabolism were measured in liver samples from 37 human fetuses ranging in gestational age from 18 weeks to term, from neonates (1-3 days) and from infants to 2 years. Glycerol kinase specific activity was constant throughout the period of fetal development examined, and was comparable to that measured in neonates and infants. However, the subcellular distribution of the activity changed markedly, being predominantly particulate in fetal samples and cytoplasmic in postnatal samples. The particulate activity had an elevated Km for glycerol. Cytoplasmic glycerol-3-phosphate dehydrogenase activity was very low in the fetal period, and then rose to adult levels during infancy. There were no kinetic differences between the fetal and postnatal activities. Mitochondrial glycerol-3-phosphate dehydrogenase activity rose somewhat after birth to near adult levels. The data indicate that glycerol can be metabolized by human fetal, neonatal and infant liver.
Cytoplasm↗
Uterine metabolism of the conscious gilt during late pregnancy.
The present study provides some metabolic features of the gravid uterus in the nonanesthetized gilt during the last fourth portion of pregnancy. Substrate and oxygen arteriovenous differences across the uterus were determined in eight gilts with chronically implanted arterial and uterine venous catheters. Glucose represents the main substrate taken up by the conceptus and glucose extraction amounts to 8.3 +/- 0.5%. By contrast, there is a constant release of lactate from the pregnant uterus. The coefficient of extraction of oxygen is 20.2 +/- 1.9%. Glucose plus lactate/oxygen quotient is high (1.3 +/- 0.2), suggesting that glucose alone is sufficient to account for the oxidative metabolism of the pig uterus. Nonesterified fatty acid and ketone body are not significantly extracted by the pig uterus whereas a significant amino acid extraction occurs in late pregnancy. Uterine uptake of amino acids depends on maternal arterial concentrations and a great part (78%) of this uterine uptake is represented by neutral amino acids and especially glutamine.
Amino Acids↗
Isoflurane has a greater margin of safety than halothane in swine with and without major surgery or critical coronary stenosis.
The fatal/anesthetic ratio (FAR) in 44 swine weighing 32.6 +/- 0.7 kg (SEM) was determined. Fatal anesthetic concentration (the numerator for FAR) was defined as the end-tidal concentration at which the pig lived at least 10 min, during experiments that involved step increments in anesthetic concentrations. Previously reported MAC was used as the "anesthetic" concentration (denominator) to determine FAR. Halothane was compared to isoflurane and the question of whether major surgery might reduce FAR was investigated. The major surgery groups included one open chest group with each volatile anesthetic studied during coronary reserve measurements, and two groups that had LAD critical coronary stenoses. Thus volatile agents were compared with vs without major surgery, and with vs without a critical coronary stenosis. The FAR for isoflurane was approximately double that of halothane. Further, addition of major surgery did not produce significant deterioration in FAR with isoflurane. In contrast, with halothane there was a significant (approximately 20%) decrease in FAR, despite values already only half that seen with isoflurane, when major surgery was added. Presence of a critical coronary stenosis was not associated with a worsened FAR for isoflurane or halothane. It was concluded that the fatal/anesthetic ratio for isoflurane in pigs is 1.9 times greater than that for halothane. Addition of major surgery did not affect FAR when isoflurane was the anesthetic but did when halothane was used. Critical coronary stenosis did not worsen FAR. Because these results are nearly identical with those reported previously in small mammals, the doubled safety margin seen with isoflurane may have clinical relevance.
Animals↗
Yeast DNA replication.
We have explored various strategies for exploiting the yeast genetic and biochemical system for understanding DNA replication. Because of the long time that has intervened between the isolation of random replication mutants of yeast and the identification of the gene products affected, an alternative approach to elucidating the molecular basis of replication has been needed. One such alternative involves purifying replication proteins, isolating the genes encoding them, and constructing the appropriate mutant from the cloned gene. We have applied this "reverse genetics" strategy to three different replication activities: DNA polymerases, single-stranded DNA binding proteins, and proteins that bind to autonomously replicating sequence (ARS) elements.
DNA Polymerase I↗
Uterine metabolism of the pregnant rabbit under chronic steady-state conditions.
The study of uterine metabolism in pregnancy under chronic steady-state conditions has been confined to large mammals and, more recently, to the guinea pig. The pregnant rabbit is of interest because of its short gestation and large litter size. We developed an indirect approach involving retrograde catheterization of the uterine venous drainage, permitting measurement of both uterine metabolic quotients and uterine uptakes. Radioactive microspheres were used to measure blood flow. A large lactate and ammonia efflux from the uterus was found. In the fed state, ketogenic substrates were taken up in small amounts. However, during starvation a significant increase in ketoacid uptake was observed with a concurrent fall in acetate uptake. There was a large glucose/oxygen quotient across the uterus, but the glucose plus lactate/oxygen quotient was comparable to that found in the sheep and guinea pig (0.6 +/- 0.1). It is apparent that in all three species studied under chronic steady-state conditions (sheep, guinea pig, and rabbit) there is a large glucose uptake associated with a net lactate production, and fuels other than glucose and lactate must be used by the uterus.
Acetates↗
Increased muscle tone during etretinate therapy.
A 40-year-old man with severe psoriasis developed painless muscle stiffness coinciding with four successive courses of etretinate therapy. Peripheral nerve block extinguished the increased muscle tone. Our patient's symptoms resembled those of the stiff-man syndrome. Increased muscle tone is a potential side effect of etretinate treatment and must be distinguished from the common musculoskeletal symptoms observed in patients taking retinoid therapy.
Adult↗
Photosensitivity and isotretinoin therapy.
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Acne Vulgaris↗
Stereoselective disposition of mexiletine in man.
The pharmacokinetics of S-(+)- and R-(-)-mexiletine and of the corresponding conjugates were investigated in six healthy young volunteers after administration of a single 200 mg oral dose of racemic mexiletine hydrochloride. The values for the distribution rate constants as well as for the elimination half-lives of the two enantiomers were similar but the AUC of the S-(+)-enantiomer was always significantly higher (P less than 0.01) than that of the opposite enantiomer. The mean R/S ratios for unchanged mexiletine in serum and in urine were 0.78 +/- 0.12 (s.d.) and 0.80 +/- 0.21, respectively. Urinary excretion of mexiletine conjugates consisted mainly of the R-(-)-enantiomer; the mean R/S enantiomeric ratio over 48 h was 9.65 +/- 3.10. Serum concentrations of the conjugates were measured in three subjects. The mean R/S AUC ratio was 2.94 +/- 0.48 and the renal clearance of the R-(-)-enantiomer was significantly higher (P less than 0.02) than that of the S-(+)-enantiomer.
Adult↗
Enoxacin compared with vancomycin for the treatment of experimental methicillin-resistant Staphylococcus aureus endocarditis.
Enoxacin administered orally was compared with vancomycin administered intravenously for the treatment of experimental methicillin-resistant Staphylococcus aureus endocarditis. The MICs and MBCs of both enoxacin and vancomycin for an inoculum of 5.0 X 10(5) CFU of the methicillin-resistant S. aureus strain per ml were 1.56 microgram/ml. With an inoculum of 10(8) CFU/ml, enoxacin at 6 micrograms/ml and vancomycin at 180 micrograms/ml resulted in similar decreases in numbers of methicillin-resistant S. aureus in broth. Methicillin-resistant S. aureus endocarditis in rabbits was treated with enoxacin at 100 mg/kg orally every 12 h or vancomycin at 30 mg/kg intravenously every 12 h for 3 or 5 days. Enoxacin treatment for 3 or 5 days and vancomycin treatment for 5 days significantly reduced bacterial counts of vegetations compared with those in untreated control rabbits after 1 day of infection. Bacterial counts of vegetations after vancomycin treatment for 3 days did not differ significantly from those of untreated controls. Bacterial counts of vegetations in the four therapeutic groups did not differ significantly from one another. In uninfected rabbits single doses of vancomycin at 30 mg/kg administered intravenously achieved much higher concentrations in serum than did single doses of enoxacin at 100 mg/kg administered orally. Enoxacin had an elimination half-life in serum that was approximately 1.5 times longer than that of vancomycin. This study demonstrated that enoxacin administered orally is as effective as vancomycin administered intravenously for the treatment of experimental methicillin-resistant S. aureus endocarditis.
Animals↗
Net substrates balance across hindlimb in conscious rabbit during late pregnancy.
The present work performed in rabbits was designed to investigate whether changes in skeletal muscle metabolism could contribute to glucose homeostasis during late pregnancy a time at which there is a large glucose demand of the gravid uterus. We therefore studied the net substrate balance of glucose, lactate, free fatty acids, and ketone bodies across the hindlimb of pregnant animals (days 24 and 30) and virgin animals. Our data show that on day 24 the basal rate of glucose uptake is similar to that observed in virgin rabbits, but it decreases by approximately 60% on day 30 despite comparable levels of blood glucose and plasma insulin at both gestational ages. A moderate hyperglycemia (20% above basal level) and hyperinsulinemia (2- to 3-fold above basal level) sustained for 80 min failed to increase glucose uptake except in virgin animals. Estimates of the contribution of substrates to oxidative metabolism indicate that free fatty acids could represent the major fuel in all groups, whereas glucose would be of minor importance especially at term. It is concluded that in pregnancy a) under normoglycemia there is a reduced insulin effect on glucose uptake and b) under moderate hyperglycemia and hyperinsulinemia the insulin resistance results from an impaired stimulation of glucose uptake. Sparing glucose from the skeletal muscle, the mother can direct more glucose toward the uterus without marked increase in her production rate.
Animals↗
Lack of skeletal radiographic changes during short-term etretinate therapy for psoriasis.
We prospectively analyzed radiographic skeletal surveys of eight patients who received etretinate therapy for psoriasis at doses ranging from 0.5 to 1.2 mg/kg/day for 6-18 months. Although subtle skeletal changes could have been obscured by some of our patients' other radiographic abnormalities, no bony changes that could be attributed to etretinate were detected in any of these patients.
Adult↗
The contribution of salivary amylase to glucose polymer hydrolysis in premature infants.
To determine whether salivary amylase of premature infants can function as a surrogate for pancreatic amylase, we evaluated its production in the infant, acid resistance, and hydrolytic potency in a simulated oropharyngeal, gastric, and intestinal environment. The activity of salivary amylase in 11 prematures varied between 1 and 33 U/ml; the isozymic profile and acid resistance of the premature salivary amylase were identical to those of the enzyme of adults. A "modular" formula containing 7 g/dl of a 14C labeled long chain glucose polymer with degrees of polymerization ranging between 18 and 29 glucose units was prepared. Salivary amylase, 1.1 U/ml, was added to this formula. The progressive breakdown of the 14C polymers as the milk was subjected to oropharyngeal, gastric, and intestinal phase environments was evaluated by quantifying the liberation of short-chain oligomers from the 14C labeled substrates. The gastric pH was varied between 2 and 5 and the gastric incubation time was either 5 or 180 min. Substantial gastric phase breakdown only occurred after 3 h of exposure at the higher pHs of 4 (12%) and 5 (32%). During the intestinal phase, salivary amylase activity resumed. Prior gastric phase pH affected ultimate intestinal phase breakdown, p less than 0.001; after 5-min gastric phases at pHs ranging from 2 to 5, the intestinal phase breakdown ranged from 17 to 55%. We conclude that the limited salivary amylase in the saliva of premature infants can produce significant glucose polymer digestion in both the stomach and small intestine but the digestion falls substantially short of that accomplished by usual concentrations of pancreatic amylase.
Adult↗
Epileptiform burst responses in ventral vs dorsal hippocampal slices.
Field potentials from area CA1 evoked by stimulation of the Schaffer collaterals were compared in dorsal and ventral hippocampal slices of rat brain. Responses were categorized into 5 response types on the basis of their morphology, ranging from simple (single spike component) to complex (multiple spike components). A higher percentage of ventral slices, compared to dorsal slices, responded with a complex morphology under normal and increased K+ concentrations. Thus, there was a significantly greater tendency for cells within the ventral hippocampus to generate burst responses.
Animals↗
Fluorescent phosphonate labels for serine hydrolases. Kinetic and spectroscopic properties of (7-nitrobenz-2-oxa-1,3-diazole)aminoalkyl methylphosphonofluoridates and their conjugates with acetylcholinesterase molecular forms.
The synthesis, kinetic, and spectral characterization of (7-nitrobenz-2-oxa-1,3-diazole)aminoethyl and (7-nitrobenz-2-oxa-1,3-diazole)aminopentyl methylphosphonofluoridate are described. These homologous organophosphorous agents contain the environmentally sensitive 7-nitrobenz-2-oxa-1,3-diazole chromophore. They inhibit acetylcholinesterase from Torpedo at rates exceeding 10(7) M-1 min-1 to form long-lived conjugates with one chromophore/80-kilodalton subunit. The intensity, position, and line width of the absorption spectra of the conjugates and reactivation kinetics in the presence and absence of the bisquaternary oxime 1,1'-trimethylene-bis(4-formylpyridinium bromide) dioxime indicate that these agents form conjugates in which the NBD-aminoalkyl moieties experience distinctive microscopic environments within the active center. NBD-aminoethyl methylphosphono-acetylcholinesterase undergoes oxime-induced as well as spontaneous reactivation at rates that are 3.6 and 35 times faster, respectively, than the corresponding rates measured for the NBD-aminopentyl conjugate. Hence, reactivation exhibits a marked dependence on structure of the methylphosphonate. Fluorescence emission at wavelengths greater than 520 nm is highly quenched and exhibits quantum efficiencies of less than 5%. Absorption maxima for the covalent NBD-aminoethyl methylphosphono-acetylcholinesterase appear at 475-480 nm while those for the corresponding NBD-aminopentyl methylphosphono-acetylcholinesterase appear at 485-490 nm. Bandwidths of the absorption maxima are substantially broader for the acetylcholinesterase adduct with NBD-aminoethyl methylphosphonofluoridate (3870 cm-1) than for the enzyme adduct with NBD-aminopentyl methylphosphonofluoridate (2870 cm-1). The CD spectrum of NBD-aminopentyl methylphosphono-acetylcholinesterase shows optical activity coincident with the shape and position of the absorption spectrum. In contrast, in addition to optically active transitions at the absorption maxima, the CD spectrum of NBD-aminoethyl methylphosphono-acetylcholinesterase shows intense optical activity at 430 nm, a wavelength region coincident with the region of spectral broadening. The spectral properties of alpha-chymotrypsin conjugates formed by reaction with the two probes are different, and the respective spectra differ also from those observed for the acetylcholinesterase conjugates. These results indicate that there is a reciprocal relationship between the structure of the probe and the structure of the active center.(ABSTRACT TRUNCATED AT 400 WORDS)
Acetylcholinesterase↗