Biomedical subjects

J Gallant

Publications and source records attributed to J Gallant.

13 recordsLinked to original sources

PubMed1979

Modern indications for cesarean section.

Total cesarean section rates and rates of various indications for primary cesarean section were reviewed for four yearly periods during the past decade. The time periods studied were chosen to follow the introduction of new obstetric practices and technologic advances in monitoring fetal condition. The total cesarean section rate increased from 6.8% to 17.1% during this time. The most common indication for primary cesarean section was cephalopelvic disproportion, which represented approximately 40% of cases during each study period. Primary cesarean section for fetal distress increased to 28.2% but has decreased over the past 2 years to a present rate of 11.7%. Primary cesarean section for breech presentation increased from 12.3% to 21%. From the perspective of this review a total cesarean section rate of 15% is predicted for the future.

Cesarean Section↗

PubMed1979

A new nucleotide involved in the stringent response in Escherichia coli. Guanosine 5'-diphosphate-3'-monophosphate.

A novel nucleotide has been detected in Escherichia coli subjected to the stringent response. However, this nucleotide does not accumulate in relA+ cells subjected to heat shock, in which guanosine 5'-diphosphate-3'-diphosphate does accumulate but stable RNA synthesis is not restricted. The intracellular level of this new nucleotide thus correlates well with control of stable RNA synthesis. Chemical and enzymatic analysis shows that the new nucleotide is guanosine 5'-diphosphate-3'-monophosphate. It is suggested that this nucleotide may play a role in stringent control of stable RNA synthesis.

Escherichia coli↗

PubMed1979

Error propagation in viable cells.

Error propagation is the process, predicted by theoretical models, whereby errors in translating the genetic code will beget fresh errors in successive generations. It has been postulated that error propagation may underly the mortality of cells which display clonal senescence. We have demonstrated the occurrence of error propagation in viable cells of E. coli during growth in a low concentration of streptomycin, a drug which promotes ribosomal ambiguity. We monitored error propagation by measuring mistranslation of a specific UAA codon, and measured viability by direct enumeration of both live and dead cells through a sensitive microscopic technique. We find that the error frequency may be artificially increased by at least an order of magnitude without generating any detectable increase in the proportion of dead cells or of cells whose descendents are doomed to clonal senescence. The error frequency increases gradually over the course of a few generations, in qualitative agreement with the notion of error propagation, and eventually stabilizes at a constant value much higher than normal. The kinetics of this increase agree quantitatively with the Hoffman-Kirkwood and Holliday formulation of error propagation, for parameter values which dictate convergence to a stable error frequency. This convergent behaviour, under conditions of enhanced mistranslation, demonstrates that the normal parameters are well removed from the region of instability in error propagation; even an order of magnitude increase in mistranslation does not tip the translation system into the unstable mode which has been postulated to underly cell senescence. Thus, the error catastrophe theory of cell senescence cannot apply to the translation system of bacteria. We have reviewed experimental data on the fidelity of translation in somatic cells of higher organisms which militate against the notion that the translation system in these cell types could be much closer to the region of instability than in bacteria. These considerations controvert the error catastrophe theory of cell senescence.

Alkaline Phosphatase↗

PubMed1979

Regulatory nucleotides involved in the Rel function of Bacillus subtilis.

We have examined the accumulation of polyphosphorylated nucleotides in Bacillus subtilis in relation to the function of the rel gene. Our results are as follows. (i) During inhibition of isoleucine activation by O-methylthreonine, wildtype B. subtilis cells accumulate unusual nucleotides with the chromatographic and chemical properties of pppApp, ppApp, pppGpp, ppGpp, pGpp, and ppGp. (ii) During the carbon source downshift elicited by inhibiting glucose uptake, we observed accumulation of the polyphosphorylated guanosine but not adenosine nucleotides. (iii) At the end of long phase in sporulation medium, we observed a small transient accumulation of the polyphosphorylated guanosine but not adenosine nucleotides. (iv) We were unable to detect a nucleotide with chromatographic behavior expected for pppAppp under any conditions. (v) The rel mutant of Swanton and Edlin (Biochem. Biophys. Res. Commun. 46-583-588, 1972) did not accumulate any of these polyphosphorylated nucleotides under any of the conditions examined. (vi) the rel mutant is unimpaired in sporulation. We conclude that one or more of the nucleotides we have detected may be involved in controlling the specificity of transcription during the stringent response, but none of them are required for sporogenesis.

Adenine Nucleotides↗

PubMed1978

A gene involved in the metabolic control of ppGpp synthesis.

A genetic locus has been identified which controls the basal synthesis of ppGpp in growing E. coli. Cells carrying a recessive allele of the relX gene have a very low concentration of ppGpp during balanced growth, and fail to accumulate ppGpp in response to carbon/energy source downshift. Moreover, the recessive relX allele renders the cells unable to grow at 42 degrees C and, when coupled with relA, makes the cells sensitive to the presence of leucine in minimal medium. RelX is cotransduced with fuc and relA and located at approximately 59.4 min on the E. coli genetic map.

Escherichia coli↗

PubMed1978

Postoperative nausea and vomiting treated with domperidone (r 33812) an open and a double-blind study.

The effect of domperidone on postoperative nausea and vomiting was evaluated in two consecutive studies. Fifty-eight patients with postoperative nausea and vomiting were included in an open pilot study and 38 other patients in a double-blind trial. In the first study 4 mg of domperidone was found to be significantly superior to 2 mg, in controlling nausea and vomiting. In the double-blind trial, vomiting recurred significantly later in domperidone than in placebo-treated patients. Side-effects were not seen nor reported in either study.

Antiemetics↗

PubMed1977

Mistranslation in E. coli.

Flagellin, the protomeric subunit of bacterial flagella, contains no cysteine. We have detected the incorporation of trace quantities of 35S-cysteine into flagellin, highly purified and then resolved by SDS polyacrylamide gel electrophoresis, to measure mistranslation in vivo. Under normal conditions, this value is about 6 X 10(-4) pmoles cysteine per pmole flagellin. This value is greatly increased during growth in low concentrations of streptomycin and neomycin, antibiotics which are known to stimulate misreading in vitro. Of the specific types of misreading which streptomycin stimulates in vitro, only misreading of the CGU and CGC arginine codons could give rise to illegitimate incorporation of cysteine. In agreement, partial arginine starvation increases the incorporation of 35S-cysteine into flagellin in a relA- mutant, with or without streptomycin, but has no such effect in its isogenic relA+ partner- Assuming from these results that 35S-cysteine incorporation into flagellin reflects misreading of CGU/C coda, we deduce a misreading probability per codon in the range of 10(-4).

Arginine↗

PubMed1977

Anomalous synthesis of ppGpp in growing cells.

In E. coli cells, accumulation of ppGpp is normally triggered by conditions that restrict the aminoacylation of tRNA or interfere with carbon/energy source metabolism; in both cases, the nucleotide's accumulation is associated with control of stable RNA synthesis and is generally believed to bring it about. We have found an anomalous situation wherein vigorously growing cells accumulate a high level of ppGpp and there is no restriction of stable RNA synthesis. This occurs when wild-type cells are shifted up from an abnormally low growth temperature to one in the optimal range (35 degrees C-40 degrees C). The effect is partly, but not entirely, dependent upon the presence of a functional relA gene product. These results appear to call into question the simpler interpretations of the role of ppGpp in the control of stable RNA synthesis.

Amino Acids↗

PubMed1977

On the translational error theory of aging.

Theoretical treatments of error feedback in translation have revealed that two different modes of behavior are possible, depending on the values of certain parameters. In mode I, the error frequency will rise steadily toward randomness, inevitably reaching whatever value is catastrophic for cell survival; the "error catastrophe" theory of aging implicitly assumes this mode of behavior. In mode II, the error frequency will converge to a stable value, which may or may not have toxic consequences. We have performed an experimental test of the behavior of the translation system in Escherichia coli cells: we altered the system's intrinsic fidelity by means of the error-promoting drug streptomycin, and monitored the kinetics of change in error frequency by means of a specific assay of one kind of mistranslation (incorporation of cysteine into flagellin). We find that the system behaves according to mode II. Moreover, E. coli cells in which the error frequency has stabilized at a value as high as 50 times greater than normal continue to proliferate, albeit abnormally slowly, and their viability is not detectably reduced. Earlier results by Gorini and his associates point in the same direction. These observations diminish the plausibility of the error catastrophe theory of aging.

Aging↗

PubMed1977

Role of the rel gene product in the control of cyclic adenosine 3',5'-monophosphate accumulation.

The presence of a relA mutant allele affects the kinetics of cyclic adenosine 3',5'-monophosphate accumulation during downshift from glucose to succinate. The nucleotide accumulates at the normal rate early in the downshift transition but continues to accumulate for a longer time in the relA mutant, leading to a two- to threefold excess by the end of the diauxic lag. Evidence is presented that this effect occurs independently of the accumulation of ppGpp.

Alleles↗

PubMed1976

A novel nucleotide implicated in the response of E. coli to energy source downshift.

When E. coli cells are subjected to energy source downshift, the accumulation of RNA (and overall cell growth) is drastically restricted within 1 to 2 min. However, the identity of the primary metabolic signal for this adjustment is a mystery. Earlier studies, and further evidence presented here, show that there is no satisfactory correlation between the sudden adjustment of RNA accumulation and the kinetics of changes in the levels of prospective signalling compounds, such as glycolytic intermediates, ppGpp, ATP, or the three adenylate nucleotides. We have discovered an unusual nucleotide, which we call the phantom spot, whose level decreases dramatically within a minute of downshift, correlating well with the adjustment of RNA accumulation. Preliminary characterization of the phantom spot indicates that it is a triphosphate derived from the guanylate pathway, and suggests that it is a form of GTP with a modification of the imidazole portion of the purine ring. We postulate that this nucleotide serves as a regulatory facsimile of ATP, linking the rate of RNA accumulation and other anabolic processes to the overall rate of phosphorylation.

Adenosine Triphosphate↗

PubMed1975

Synthesis and turnover of ribosomal ribonucleic acid in guanine-starved cells of Escherichia coli.

The relationship between the rate of RNA accumulation and the level of guanosine triphosphate was examined. Cells auxotrophic for guanine show a 6-fold drop in the intracellular level of GTP in response to the exhaustion of the exogenous guanosine supply. Contraction of the GTP pool results in a 2.5-fold reduction in the rate of RNA synthesis and the cessation of RNA accumulation. The decrease in the rate of RNA synthesis is seen to occur at the level of chain elongation. Analysis of RNA made in guanine-starved cells by competition-hybridization and sucrose gradient sedimentation suggests that the turnover of newly synthesized ribosomal RNA accounts for the observed failure of RNA to accumulate.

Escherichia coli↗

PubMedDate not supplied

Domperidone in the treatment of postoperative vomiting: a double-blind multicenter study.

Domperidone was compared with placebo in a multicenter double-blind study of 116 patients (15 to 80 years) with postoperative vomiting. After vomiting had occurred, the patients received either domperidone 10 mg or placebo IV. Patients were then followed for at least 6 hours or until a 2nd injection of domperidone 10 mg from an open supply was needed. The period of time until an additional injection was registered and compared between the 2 treatment groups. Fifty-nine percent of the placebo patients needed a 2nd injection before the end of the 6-hour follow-up, compared with only 35% of the domperidone patients (p less than 0.05). When a 2nd injection was required, the time elapsed before it was needed was longer (p = 0.01) in the domperidone group (median 150 minutes) than in the placebo one (median 120 minutes). There were no significant side-effects.

Antiemetics↗