Protein losing enteropathy-hepatic fibrosis syndrome in Saguenay-Lac St-Jean, Quebec is a congenital disorder of glycosylation type Ib.
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Biomedical subjects
Publications and source records attributed to C Prevost.
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Mutations at the hexosaminidase A (HEXA) gene which cause Tay-Sachs disease (TSD) have elevated frequency in the Ashkenazi Jewish and French-Canadian populations. We report a novel TSD allele in the French-Canadian population associated with the infantile form of the disease. The mutation, a G-->A transition at the +1 position of intron 7, abolishes the donor splice site. Cultured human fibroblasts from a compound heterozygote for this transition (and for a deletion mutation) produce no detectable HEXA mRNA. The intron 7 + 1 mutation occurs in the base adjacent to the site of the adult-onset TSD mutation (G805A). In both mutations a restriction site for the endonuclease EcoRII is abolished. Unambiguous diagnosis, therefore, requires allele-specific oligonucleotide hybridization to distinguish between these two mutant alleles. The intron 7 + 1 mutation has been detected in three unrelated families. Obligate heterozygotes for the intron 7 + 1 mutation were born in the Saguenay-Lac-St-Jean region of Quebec. The most recent ancestors common to obligate carriers of this mutation were from the Charlevoix region of the province of Quebec. This mutation thus has a different geographic centre of diffusion and is probably less common than the exon 1 deletion TSD mutation in French Canadians. Neither mutation has been detected in France, the ancestral homeland of French Canada.
LF 2-0254 is a 1,4-dihydropyridine calcium antagonist with a slow onset of action. The pharmacokinetics of [14C]LF 2-0254 were studied in rats and dogs. A sensitive high-performance liquid chromatographic method using liquid scintillation counting was developed for the quantitation of labelled LF 2-0254 in plasma. The peak height of the internal standard in the chromatogram was measured by UV detection and the mobile phase containing the chromatographic peak of [14C]LF 2-0254 was collected and counted for radioactivity. The concentration of labelled drug in the plasma was then determined using a calibration graph constructed from the determination of [14C]LF 2-0254 of known specific activities. The limit of determination was dependent on the specific activity of the drug administered. This method permits the measurement of the radioactive drug in biological fluids.
For psychiatric patients treated in general hospitals, the prospective payment system does not differentiate between patients treated in medical-surgical wards and patients treated in psychiatric units. In particular, the system uses a single length-of-stay norm for both kinds of patients, even though psychiatric patients in medical-surgical units have shorter stays. The authors document major differences in length of stay and hospital charges for both groups of patients in relation to selected patient and hospital characteristics. They conclude that the current reimbursement procedures systematically overpay for stays in nonpsychiatric units and underpay for stays in psychiatric units, and they suggest mechanisms for partly reducing such inequities.
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Metrizamide computed tomographic cisternography was used to examine 27 patients (19 males and eight females, 14-59 years old) clinically suspected of having cerebrospinal fluid fistulae with rhinorrhea. Twenty-one fistulae were traumatic and six were spontaneous. Five to 6 ml of metrizamide (or lopamidol, two cases) were injected by lumbar puncture at a concentration of 185-200 mg I/ml for direct coronal and axial computed tomographic sections of the skull base. Cerebrospinal fluid rhinorrhea was present at the time of examination in 12 of 27 cases. Results were evaluated according to three criteria: (1) metrizamide passage through the bony and dural defect; (2) demonstrable site of the fracture and/or bony defect; and (3) metrizamide visualized within a paranasal sinus, nasal cavity, or cotton pledget. The examination was considered positive when criterion 1 alone was present and when 2 and 3 were associated. In 15 of 27 cases, cisternography was positive, with the exact site of cerebrospinal fluid leakage demonstrated in 10 patients. In six cases, the results were not definitive; only one of the criteria (2 or 3) was fulfilled. In six cases, cisternography was normal. Seventeen patients underwent surgery. The site of cerebrospinal fistulae was ethmoidal in nine cases, frontoethmoidal in seven, sphenoidal in two, and sphenoethmoidal in one. The relative value of metrizamide computed tomographic cisternography compared with other diagnostic studies, polytomography, positive or negative contrast studies, and radionuclides, is discussed. Diagnostic pitfalls include artifacts and partial volume effect.
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1. The intermediary metabolism of two strains of Escherichia coli has been examined. One strain (Q22) exhibits acute transient repression of beta-galactosidase synthesis when glucose is supplied to cells growing on glycerol; the other strain (W3110) does not. The two strains do not differ genetically in their lac operons. 2. Strain Q22 uses about twice as much glucose as strain W3110 per unit of cell mass produced. 3. Pentose phosphate-cycle activity in the presence of glucose is much stronger in strain Q22 than in strain W3110. 4. In strain Q22 the pool sizes of glucose 6-phosphate, 6-phosphogluconate, fructose 1,6-diphosphate and NADPH increase when glucose is added to cells growing on glycerol, and beta-galactosidase synthesis is severely inhibited. After about 1hr. the synthesis of beta-galactosidase is partly resumed, and the pool sizes of the four compounds fall. ATP, NADH and several other phosphorylated compounds show no concentration changes. 5. These concentration changes do not occur in strain W3110, in which beta-galactosidase synthesis is only rather weakly repressed by glucose. 6. It is suggested that repression of enzyme synthesis by glucose requires the rapid operation of the pentose phosphate cycle, and is mediated by one of the four substances whose concentration rises and later falls in strain Q22. A definite choice of effector from among these four possibilities cannot at present be made.
1. Repression by glucose of beta-galactosidase synthesis is spontaneously reversible in all strains of Escherichia coli examined long before the glucose has all been consumed. The extent of recovery and the time necessary for reversal differ among various strains. Other inducible enzymes show similar effects. 2. This transient effect of glucose repression is observed in constitutive (i(-)) and permease-less (y(-)) cells as well as in the corresponding i(+) and y(+) strains. 3. Repression is exerted by several rapidly metabolizable substrates (galactose, ribose and ribonucleosides) but not by non-metabolized or poorly metabolized compounds (2-deoxyglucose, 2-deoxyribose, phenyl thio-beta-galactoside and 2-deoxyribonucleosides). 4. The transient repression with glucose is observed in inducible cells supplied with a powerful inducer of beta-galactosidase synthesis (e.g. isopropyl thio-beta-galactoside) but not with a weak inducer (lactose); in the latter instance glucose repression is permanent. Diauxic growth on glucose plus lactose can be abolished by including isopropyl thio-beta-galactoside in the medium. 5. In some strains phosphate starvation increases catabolite repression; in others it relieves it. Adenine starvation in an adenine-requiring mutant also relieves catabolite repression by glycerol but not that by glucose. Restoration of phosphate or adenine to cells starved of these nutrients causes a pronounced temporary repression. Alkaline-phosphatase synthesis is not affected by the availability of adenine. 6. During periods of transient repression of induced enzyme synthesis the differential rate of RNA synthesis, measured by labelled uracil incorporation in 2min. pulses, shows a temporary rise. 7. The differential rate of uracil incorporation into RNA falls during exponential growth of batch cultures of E. coli. This is equally true for uracil-requiring and non-requiring strains. The fall in the rate of incorporation has been shown to be due to a real fall in the rate of RNA synthesis. The significance of the changes in the rate of RNA synthesis is discussed. 8. A partial model of catabolite repression is presented with suggestions for determining the chemical identification of the catabolite co-repressor itself.
Prevost, C. (University of California, Berkeley), and V. Moses. Action of phenethyl alcohol on the synthesis of macromolecules in Escherichia coli. J. Bacteriol. 91:1446-1452. 1966.-A kinetic study of the effects of various concentrations of phenethyl alcohol on the synthesis of ribonucleic acid (RNA), deoxyribonucleic acid (DNA), protein, and beta-galactosidase in Escherichia coli has confirmed that RNA synthesis, rather than DNA synthesis, is first and most affected by phenethyl alcohol. The presence of inducer did not protect beta-galactosidase synthesis from inhibition by phenethyl alcohol. Little preferential inhibition of beta-galactosidase synthesis was observed; this is in contrast to the severe catabolite repression which results from partial inhibition of total protein synthesis caused by chloramphenicol or starvation for a required amino acid. We found no evidence that messenger RNA synthesis was inhibited to a greater extent than total RNA synthesis.
We compared the ability of two different diets containing 6 per cent of maize oil and 6 per cent of fish oil to modify: firstly the enzyme induction by phenobarbital and secondly the phenobarbital hydroxylation by the liver either in vivo or during in vitro perfusions. The presence of fish oil in the diet increased the cyt P 450 content and the bilirubin glucuronosyl transferase activity. The two induction effects promoted by the association of the phenobarbital treatment and the eating of the fish oil were not additive and it was found that the phenobarbital induction effect was decreased by the fish oil consumption. Phenobarbital and p-hydroxyphenobarbital kinetics were different in the two groups of animals. Phenobarbital was more slowly eluted in the fish oil fed than in the maize oil fed rats while p-hydroxyphenobarbital was more slowly eluted by the fish oil-fed rat livers.
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