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Biomedical subjects

R E Glass

Publications and source records attributed to R E Glass.

At least 55 records · Page 3Linked to original sources
PubMed1985

Internal fistulas in Crohn's disease.

There is doubt about the timing of surgery for patients with internal fistulas in Crohn's disease. Although immediate operative intervention for all patients has been advocated, such a policy has not always been followed at St. Mark's Hospital. Between 1971 and 1982, 83 internal fistulas were identified in 59 patients with Crohn's disease. Fifty-nine fistulas arose primarily from the small intestine and involved another segment of the bowel, five were between large bowel and duodenum, and three between areas of large bowel. Sixteen fistulas (ten from ileum and six from large bowel) involved the bladder. Thirty-six patients with 54 fistulas underwent immediate surgical treatment. Fifteen patients with 20 fistulas required surgery later. There was one postoperative death among the 51 patients treated surgically and one late death unrelated to the treatment of the fistula. Of the remaining 49 surgically treated patients, 46 were traced and remain well, six after further surgery. Eight patients with nine fistulas (four involving the bladder) were treated at St. Mark's without operation. One later required surgery elsewhere for an enterocutaneous fistula, but the remaining seven patients are well. This study suggests that the presence of an internal fistula, even if it involves the bladder, is not an absolute indication for immediate surgery and that the severity of the symptoms should dictate the treatment policy.

Adolescent↗
PubMed1985

Autogenous posttranscriptional regulation of RNA polymerase beta and beta' subunit synthesis in Escherichia coli.

Bacterial strains carrying poorly suppressed amber mutations in the RNA polymerase beta subunit gene (rpoB) exhibit regulatory compensation. This compensation allows these strains to produce an adequate content of RNA polymerase to support a near normal rate of growth despite the poorly suppressed amber mutation. The primary compensatory mechanism permitting the elevated expression functions by permitting a much more efficient (up to threefold) loading of ribosomes at the beta cistron translation initiation site on the mRNA. This result supports the concept that the production of beta and beta' RNA polymerase subunits are autogenously regulated at the level of mRNA translation; this translational mechanism is clearly distinct from the transcriptional mechanism regulating beta and beta' expression described previously (P. P. Dennis, Proc. Natl. Acad. Sci. U.S.A. 74:5416-5420, 1977).

DNA-Directed RNA Polymerases↗
PubMed1984

Genetic studies on the beta subunit of Escherichia coli RNA polymerase. VI. A redundant region in the beta polypeptide.

A single species of RNA polymerase is responsible for the transcription of genetic material in Escherichia coli; and, each component of this essential enzyme is encoded by a single gene. Nevertheless, we report the characterisation of a viable deletion mutant lacking about 165 bp in the region coding for residues 965 to 1143 of the beta subunit of this enzyme. The foreshortened beta polypeptide appears to function as normal, suggesting that this region is, in fact, non-essential with regard to the usual functions of E. coli RNA polymerase.

Amino Acid Sequence↗
PubMed1984

Genetic studies on the beta subunit of Escherichia coli RNA polymerase. IV. Structure-function correlates.

We have isolated a set of strains that synthesise 331 potential variants of E. coli DNA-dependent RNA polymerase making use of nonsense suppression of amber mutations in the beta structural gene; rpoB. Translational mapping, together with the effect of known amino acid substitutions, has allowed us to locate sites on the beta polypeptide involved in transcription termination, stringent response and resistance to the antibiotic rifampicin. In general, the C-terminal quarter appears to be less affected by such single amino acid exchanges than the rest of beta. These studies permit for the first time structure-function correlates for the beta subunit of RNA polymerase.

Bacterial Proteins↗
PubMed1983

Relaxed mutants of Escherichia coli RNA polymerase.

Unusual guanosine nucleotides synthesised during amino acid or energy source starvation are thought to be the effectors of the stringent response. In vitro experiments suggest that the magic spot compounds alter transcription specificity of RNA polymerase by binding to the enzyme. However, there is no good in vivo evidence for such an interaction. We define sites on the beta-subunit of RNA polymerase which, when altered, yield E.coli mutants apparently insensitive to the presence of ppGpp.

DNA-Directed RNA Polymerases↗
PubMed1983

Genetic studies on the beta subunit of Escherichia coli RNA polymerase. III. Analysis of low-level rifampicin-resistant mutants.

Spontaneously-occurring rifampicin-resistant mutants that survive on low (20 micrograms ml-1) but not high drug concentrations (200 micrograms ml-1) have been isolated. One such mutation appears to map close to residue 650 on the beta structural gene. RNA polymerase from low-level resistant strains shows an intermediate response to rifampicin in vitro: both the association and dissociation rates of the antibiotic are markedly reduced. Continued expression of this unusual phenotype upon introduction of a high-level resistance allele is described in terms of DNA blockade.

DNA-Directed RNA Polymerases↗
PubMed1983

Whole-body protein turnover before and after resection of colorectal tumours.

1. The rate of whole-body nitrogen flux, protein synthesis and protein breakdown were measured in patients with colorectal cancer (Dukes A-C) just before and 12 weeks after surgical removal of the tumour. The rates were determined from the urinary excretion of 15N in ammonia and in urea over a 9 h period after an oral dose of [15N]glycine. 2. The food intake during the 2 study days was identical for individual patients. The amount each received was determined from measurement of their intake of food ad libitum on the day preceding the pre-operative study and was consumed in six equal portions every 2 h during the experimental period. 3. No significant differences in the rates of nitrogen flux, protein synthesis and protein breakdown were found before and after tumour resection, whether calculated from the excretion of 15N in ammonia or in urea. Some changes in flux, both increases and decreases, were observed in individual patients after tumour removal but these could not be related to classification of the tumour, or to the presence of pre-operative anorexia or weight loss. 4. The results suggest that the primary tumour itself does not alter the overall rate of protein metabolism in the whole body.

Adenocarcinoma↗
PubMed1982

Genetic studies on the beta subunit of Escherichia coli RNA polymerase. I. The effect of known, single amino acid substitutions in an essential protein.

The use of five different nonsense suppressors, in conjunction with a collection of 95 independent, spontaneously-occurring amber mutants affecting expression of rpoB, allows the generation of a maximum of 475 potential variants of the beta subunit of E. coli RNA polymerase, each carrying a known amino acid substitution at a particular site. The effect of these amino acid exchanges has been investigated in vivo. A significant majority (363/475) of substitutions lead to cellular death and altered properties--temperature sensitivity, apparently altered transcription termination and a changed stringent response--indicating that RNA polymerase function (unlike that of dispensable proteins) is extremely sensitive to such single site changes.

DNA-Directed RNA Polymerases↗
PubMed1982

Genetic studies on the beta subunit of Escherichia coli RNA polymerase. II. Evidence that large N-terminal amber fragments of the beta subunit interfere with RNA polymerase function.

A collection of 95 independent, spontaneously-occurring mutants carrying amber lesions that affect expression of the beta gene, rpoB, has been isolated (see accompanying paper (Nene and Glass 1982)). Certain rpoB amber mutations act in trans, preventing a functional allele present on an F' plasmid from acting at high temperature. Two such temperature-sensitive rpoB(Am) strains are shown to produce large, N-terminal amber fragments. The possibility that these truncated polypeptides are the cause of this transdominant conditional-lethal phenotype is supported by analysis of fragment levels in thermoresistant survivors: the nonsense fragments are degraded at a significantly faster rate (half-lives 1.4- to 2.6-fold reduced) in Ts+ derivatives likely to carry second-site mutations within rpoB. We suggest that the beta fragments interfere with RNA polymerase function by interacting with one or more of the polymerase subunits.

DNA-Directed RNA Polymerases↗
PubMed1982

Deletion analysis of essential genes of Escherichia coli: investigation of the btuB-rpoBC interval.

A method is described for deletion mapping of essential genes in Escherichia coli. It involves the isolation of secondary-site insertions of lambda cI857plac5 into an F' plasmid. The transposed lacZ gene is useful both for the ready screening of plasmid-phage cointegrates and for rapid analysis of deletions that extend from the site of phage integration into the bacterial genes carried on the substituted plasmid. Such deletions may be used to 'hook-up' bacterial cistrons to the powerful lac promoter. We report the application of this technique to the study of the btuB-rpoBC interval, a cluster of genes encoding components of the transcription-translation apparatus.

Bacteriophage lambda↗
PubMed1982

Analysis of btuB receptor function by use of nonsense suppression.

Informational suppression of btuB nonsense mutants allows the study of the effect of known, single amino acid substitutions on receptor function. We found that ligand uptake is largely unaffected by such amino acid changes. The few instances in which certain substitutions destroyed sensitivity to the two lethal agents (phage BF23, colicin E3) without affecting vitamin B12 uptake suggest a common region on the btuB receptor involved in the binding of these proteinaceous agents.

Colicins↗
PubMed1981

Direct measurement of absolute suppressor efficiency.

We have devised a system for measuring the degree of translational readthrough past a nonsense mutation which is based upon the quantitation of the two translation products, the suppressed polypeptide and the nonsense fragment. The absolute efficiency of four different amber suppressors (Su1, Su2, Su3, and Su7) has been determined at two unique amber sites in the structural gene for the beta subunit of Escherichia coli RNA polymerase.

DNA-Directed RNA Polymerases↗
PubMed1978

Cancer of the rectum following colectomy and ileorectal anastomosis for ulcerative colitis.

The case notes of all patients treated for ulcerative colitis by colectomy and ileorectal anastomosis at the Gordon Hospital under the care of Mr S. O. Aylett from 1952 to 1976 have been reviewed. Three hundred and seventy-four patients left hospital with an ileorectal anastomosis and have been followed for periods up to 23 years. Twenty-two patients are known to have developed a carcinoma of the rectum. Within 10 years of the onset of the disease, no rectal carcinoma was found in 3534 patient-years. The risk was 1 in 185 patient-years between the tenth and twentieth years and 1 in 115 patient-years between the twentieth and thirtieth years. The cumulative risk was 6 per cent (+/- 2 per cent) at 20 years and 15 per cent (+/- 4 per cent) at 30 years. The need for meticulous follow-up is emphasized. The finding of dysplasia in rectal mucosal biopsies will, it is hoped, identify the patient at particularly high risk and enable rectal excision to be undertaken before carcinoma develops.

Adolescent↗
PubMed1978

Urethral injury and fractured pelvis.

In 333 consecutive cases of fractures of the pelvis admitted as emergencies to one hospital 53% were in males, of whom 34 had suspicious clinical signs of urethral or vesical injury. In 15 patients catheterisation was performed uneventfully and in no case did this make the injury worse; in 8 an attempt at primary realignment was performed, resulting in 4 cases without any stricture, and 2 who needed annual dilation only. In 4 additional cases associated laceration of the bladder was repaired of which one had no stricture and 2 needed infrequent dilatations. In a further 41 cases a catheter was used and led to no strictures. Among 67 males with post-traumatic urethral injuries caused by pelvic fracture the best results were seen when the 2 ends were approximated. In 4 cases a stricture was prevented entirely, and in 17 others it led to an easy urethroplasty. Difficult strictures occurred in severe injuries with uncorrected displacement of the soft parts. Where feasible, early surgical repair appears to give the best chance of minimising the severity of subsequent urethral stricture.

Fractures, Bone↗