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Biomedical subjects

S M Bell

Publications and source records attributed to S M Bell.

At least 73 records · Page 4Linked to original sources

The prevalence of inducible beta-lactamase in clinical isolates of Yersinia enterocolitica.

In a prevalence study, 100 clinical isolates of Yersinia enterocolitica belonging to biotypes 1A, 3 and 4 isolated in Australia were examined for the induction of beta-lactamase in broth at 28 degrees C using imipenem as an inducer. An increase in beta-lactamase activity ranging from 15 to 93 fold was observed with all 36 isolates of biotypes 1A and 3 confirming that both enzyme B and enzyme "B-like" in biotype 3 and biotype 1A Yersinia enterocolitica were readily inducible. By contrast, imipenem failed to induce beta-lactamase in any of the 64 isolates of Yersinia enterocolitica belonging to biotype 4.

Enzyme Induction↗

Effect of prone versus supine patient positioning on pelvic magnetic resonance image quality.

RATIONALE AND OBJECTIVES: Magnetic resonance imaging (MRI) of the pelvis in the prone position has been proposed as a means of reducing motion-related image blurring. The authors performed a randomized controlled trial to determine if patient positioning affects image quality. METHODS: All women undergoing pelvic MRI during a 7-month period, who could lie both prone and supine, were randomized to the supine or prone position. The quality of axial T2-weighted spin-echo images was rated by two radiologists using a 1-to-4 scale (1 = marked blurring to 4 = sharp definition of pelvic structures). RESULTS: Of 78 eligible women, 61 were randomized. Two patients could not complete the examination. The mean image quality rating of 2.8 for the 32 patients imaged prone was not significantly different from the mean rating of 2.9 for the 27 patients imaged supine (P = .5, Mann-Whitney U test). CONCLUSION: Patient positioning did not significantly affect pelvic MRI quality. The choice of patient position should be based on other considerations, such as patient comfort or ease of patient positioning.

Adult↗

Beta-lactamase induction by imipenem in Yersinia enterocolitica.

Five strains of Yersinia enterocolitica belonging to 5 different biotypes were induced to beta-lactamase production with imipenem in broth culture at 28 degrees C. Strains belonging to biotypes 1A, 1B, 2 and 3 showed a 26 to 73 fold increase in beta-lactamase activity after 180 min in the presence of 0.5 mg/L imipenem. Biotype 4 strain, by contrast, did not show obvious enhancement of its beta-lactamase activity in the same experiments. Enzyme B in biotypes 1B, 2 and 3 and enzyme "B-like" in biotype 1A were shown to be responsible for the increase of the beta-lactamase activity, but neither enzyme nor any similar enzyme was found to be present in biotype 4 strain.

Culture Media↗

Improving surveillance of infectious diseases in New South Wales.

OBJECTIVE: To determine the feasibility of laboratory reporting of infectious diseases and to compare the value of this system with the existing medical practitioner notification system. DESIGN: A sample of notifications was selected from medical practitioner notifications and was compared for both completeness and timeliness of notification with a sample of notifications obtained through the Laboratory Infectious Diseases Surveillance Project. SETTING: The New South Wales Health Department and the Public Health Unit of the Eastern Sydney Area Health Service. PARTICIPANTS: Medical practitioners forwarding notifications of infectious diseases to the New South Wales Health Department and laboratories participating in the Laboratory Infectious Diseases Surveillance Project. MAIN OUTCOME MEASURES: We counted the number of infectious diseases reported by medical practitioners and participating laboratories and estimated the proportion of these diseases which were common to both sources of data. We also estimated the time taken between the diagnosis of a notifiable infectious disease and the receipt of the notification by the Medical Officer of Health. RESULTS: There was substantial underreporting of notifiable infectious diseases by medical practitioners. During the study there were 461 cases of a notifiable disease reported by either medical practitioners or by participating laboratories. Of these cases, 75% were reported only by laboratory staff, 20.2% were reported by medical practitioners alone and 4.8% of cases were reported by both laboratory staff and medical practitioners. The Medical Officer of Health received the reports from the participating laboratories within a significantly shorter time than the notifications from medical practitioners. CONCLUSION: The use of infectious disease notifications by laboratories can substantially improve the surveillance of infectious diseases.

Communicable Disease Control↗

c-Ki-ras gene mutations in dysplasia and carcinomas complicating ulcerative colitis.

One hundred and nine samples comprising carcinomas, adenomas, dysplastic, inflamed and normal mucosa from patients with sporadic colon cancer and ulcerative colitis (UC) were analysed for c-Ki-ras mutations. DNA was extracted from archival paraffin-embedded material, amplified using the polymerase chain reaction (PCR) and the PCR products analysed using restriction enzyme digestion. Forty-two per cent (14/33) of the sporadic carcinoma controls contained Ki-ras codon 12 mutations in contrast to 24% (8/33) of ulcerative colitis carcinomas. A significantly higher c-Ki-ras mutation rate was observed in rectal carcinomas (72%) in comparison to colonic carcinomas (28%) in control patients (P less than 0.04), while the opposite was observed in UC patients. The difference between the incidence of c-Ki-ras mutations in rectal carcinomas in UC (9%) and in sporadic rectal carcinomas (72%) was also significant (P less than 0.01). This lower prevalence rate and different site distribution of c-Ki-ras mutations in UC carcinomas compared to sporadic carcinomas suggests that specific genetic differences may underlie the causation of carcinomas arising in these situations.

Codon↗

Biotype and antibiotic sensitivity of 100 clinical isolates of Yersinia enterocolitica.

One hundred clinical isolates of Yersinia enterocolitica were biotyped, serotyped and tested for in-vitro sensitivity to seven beta-lactam antibiotics and six other antibiotics. Twenty-four of the isolates belonged to Niléhn's and Wauters' biotype 1A, 12 to biotype 3 and 64 to biotype 4. No biotypes 1B or 2 strains were found. All isolates were sensitive to chloramphenicol, ciprofloxacin, gentamicin, tetracycline, trimethoprim and all but one to sulphafurazole. All were resistant to ampicillin with MIC's ranging from 32 to 256 mg/L, but were susceptible to ticarcillin/clavulanic acid and imipenem. With other beta-lactam agents there were different patterns of sensitivity, specific to each of the three biotypes. All biotype 4 strains were resistant to carbenicillin and ticarcillin but sensitive to amoxycillin/clavulanic acid and cefoxitin. Biotype 3 strains, by contrast, were sensitive to carbenicillin and ticarcillin but resistant to amoxycillin/clavulanic acid and cefoxitin, whilst biotype 1A strains were resistant to each of these four beta-lactam agents.

Anti-Bacterial Agents↗

A study of the beta-lactamases of 100 clinical isolates of Yersinia enterocolitica.

The intracellular beta-lactamases of 100 distinct clinical isolates of Yersinia enterocolitica were examined, to investigate the effect of selected beta-lactam agents on the enzymes. The enzyme inhibition profiles obtained were specific to each of the three biotypes 1A, 3 and 4. Biotype 4 strains elaborated only one beta-lactamase with a pI of 8.3 corresponding to the carbenicillin-hydrolysing beta-lactamase enzyme A of Cornelis & Abraham. Biotype 3 strains also produced a single beta-lactamase with a pI of 5.4-5.6 corresponding to enzyme B, the chromosomally mediated inducible cephalosporinase. Two beta-lactamases were found in biotype 1A strains, one was identical to enzyme A and the other, although showing a slight difference in pI to enzyme B, was similar to this enzyme in other respects. The differences in the distribution of enzyme A and enzyme B in strains of Y. enterocolitica belonging to the biotypes 1A, 3 and 4 isolated in Australia, explain the different patterns of susceptibility to beta-lactam antibiotics.

Anti-Bacterial Agents↗

Plasminogen activator gene expression is induced by the src oncogene product and tumor promoters.

Secretion of urokinase-type plasminogen activator (uPA) by chicken embryo fibroblasts (CEF) is increased approximately 50-fold following transformation by Rous sarcoma virus (RSV). Using a cloned and fully sequenced chicken uPA cDNA probe, we have established that this increase in plasminogen activator production can be largely accounted for by an increase in cellular uPA mRNA. CEF contained on average less than 1 molecule of uPA mRNA/cell, whereas RSV-CEF contained 25-60 molecules/cell. The increase in cellular uPA mRNA levels was dependent on the activity of the RSV-encoded transforming protein, protein-tyrosine kinase pp60v-src. Cells infected with an RSV mutant encoding a temperature-sensitive form of the src protein (ts-NY68) contained low uPA mRNA levels when cultured at the nonpermissive temperature and high uPA mRNA levels when maintained at the permissive temperature. Temperature shift studies with tsNY68-CEF demonstrated that changes in pp60v-src activity rapidly altered uPA mRNA levels; the uPA mRNA content of total RNA extracts increased and decreased with half-time kinetics of 3-5 h. Serine/threonine-specific protein kinases also appear to modulate uPA mRNA levels in CEF cultures. Exposure of CEF and RSV-CEF for 24 h to the protein kinase C activating agent phorbol myristate acetate (PMA) increased cellular uPA mRNA levels to 20 and 260 molecules/cell, respectively. These data are consistent with the previously observed synergism between RSV and PMA in increasing plasminogen activator secretion. Nuclear run-on transcription analyses established that both RSV and PMA increase cellular uPA mRNA levels by way of increased uPA gene expression.

Animals↗

The chicken urokinase-type plasminogen activator gene.

The chicken urokinase-type plasminogen activator (uPA) cDNA and gene have been isolated and the complete nucleotide sequence of each established. cDNA sequence and Northern blot RNA analysis indicate that the chicken uPA mRNA is approximately 2500 nucleotides in size and contains a large 3'-noncoding region (998 nucleotides). The predicted amino acid sequence of the chicken uPA primary translation product (434 residues) suggests a domain architecture comparable to the mammalian uPA proteins with the form: (i) signal peptide, (ii) growth factor domain (GF), (iii) kringle domain (K), and (iv) serine protease domain (C). The overall sequence identity between the chicken and human proteins is 43.1%, with 56.3, 48.5, and 45.6% identity in the GF, K, and C domains, respectively. The chicken uPA gene is similar to the mammalian uPA genes in both size (8158 base pairs between transcription initiation and polyadenylation sites) and organization (11 exons). However, the sequence of the chicken uPA gene is similar to the mammalian uPA genes only within the protein-coding portions of exons. The transcription initiation site is flanked by a remarkably G/C-rich region (77% between nucleotides -1 and -300) which contains a TATA element and several potential transcription factor Spl-binding sites. The promoter region also contains several repeat elements, including two 11-nucleotide repeats that encompass six potential transcription factor AP-2-binding sites. This work provides a foundation for exploring the mechanism(s) by which protein-tyrosine kinase pp60v-src and protein kinase C modulate uPA gene transcription.

Amino Acid Sequence↗

A DNA topoisomerase II-independent route for novobiocin-mediated resistance to DNA binding agents.

The coumermycin antibiotic novobiocin is currently under investigation as an agent that can modify the toxicity of various anti-cancer drugs, potentially via one of its many pharmacological effects: namely, the interference with type II DNA topoisomerase function. This paper investigates the ability of novobiocin to modify the cellular/nuclear accumulation and toxicity of two types of DNA binding agents (the minor groove ligand Hoechst 33342 and the intercalating anthracycline Adriamycin). We report that novobiocin reduces the cytotoxicity of both agents and that this can be attributed to a reduction in cellular and, consequently, nuclear accumulation of these agents rather than to any effect on cellular export. The antibiotic was also active (at non-toxic concentrations) in delaying the progression of cells into S phase and G2 phase. This potential for novobiocin to effect rescue from toxicity by disturbance of the delivery of a drug to a potentially important intracellular target, together with the provision of an extended period of cellular recovery prior to the commitment of cells to G2 + M phase, should be recognised in the design of combination chemotherapy.

Animals↗

Determination and importance of varicella immune status of nursing staff in a children's hospital.

A survey of nurses at the Prince of Wales Children's Hospital was conducted to determine the prevalence of immunity to varicella-zoster virus (VZ) as defined by enzyme immunoassay (EIA), and to establish the value of history as a predictor of immunity. Of the 209 nurses surveyed, 51% could recall suffering VZ infection, and with a single exception, all of this group were immune. However, despite a 95% prevalence of immunity among all nurses, 46% of those found to be immune by EIA could not recollect having VZ infection. In the event of a hospital VZ outbreak, the latter group, without serological testing, would thus need to be regarded as susceptible, and this would create a major logistical problem in staffing the affected areas. We suggest, to minimize this cause of disruption to services, that all paediatric staff with patient contact should be asked at the time of recruitment if they recall suffering VZ infection. Those who give a positive response may be considered immune, but all other staff should have their immune status assessed by EIA at the earliest opportunity.

Adult↗

Characterization of the cDNA coding for mouse plasminogen and localization of the gene to mouse chromosome 17.

A full-length cDNA coding for mouse plasminogen has been isolated and characterized. The cDNA is 2720 bp in length (excluding the poly(A) tail) and contains a 24-bp 5' noncoding region, an open reading frame of 2436 bp, and a 3' noncoding region of 257 bp. The open reading frame codes for 812 amino acids and includes a signal peptide that is likely 19 amino acids in length and the mature protein of 793 amino acids. The calculated Mr of mouse plasminogen is 88,706 excluding carbohydrate. There are two potential N-linked carbohydrate addition sites; one of which is glycosylated in human, bovine, and porcine plasminogens. Mouse plasminogen was found to contain two additional amino acids compared to the human protein. In addition, mouse and human plasminogens were found to be 79 and 76% identical at the protein and DNA levels, respectively. Analysis of the segregation of two allelic forms, Plgb and Plgd, of plasminogen DNA in three sets of recombinant inbred strains has allowed the localization of the mouse plasminogen gene to the proximal end of mouse chromosome 17 within the t complex and close to the locus D17Rp17. The Plg gene is deleted in the semidominant deletion mutant, hair-pintail (Thp).

Alleles↗

Involvement of DNA topoisomerase II in the selective resistance of a mammalian cell mutant to DNA minor groove ligands: ligand-induced DNA-protein crosslinking and responses to topoisomerase poisons.

A mutant murine cell line has previously been reported to be resistant to the AT-specific DNA minor groove ligand 2',5'-bi-1H-benzimidazole, 2',(4-ethoxyphenyl)-5-(4-methyl-1-piperazinyl), trichloride (Ho33342), due to an enhanced capacity to remove ligand molecules from cellular DNA via a pathway which can be blocked by DNA topoisomerase poisons. We have studied the relationship between ligand resistance and DNA topoisomerase II activity. The cross-sensitivity patterns of the mutant were examined for covalently (anthramycin) and non-covalently (distamycin A) binding minor groove ligands, and DNA intercalating [adriamycin, mitoxantrone and 4'-(9-acridinylamino)methanesulphon-m-anisidide (mAMSA)] and non-intercalating (VP16-213) topoisomerase II poisons. The mutant was cross-resistant to distamycin A alone. The mutant showed no abnormality in: (i) the in vitro decatenation activity of topoisomerase II, (ii) VP16-213 or mAMSA induced protein-DNA cross-linking activities in nuclear extracts, (iii) 'cleavable complex' generation (or DNA strand scisson) in intact cells exposed to topoisomerase poisons. Ho33342 and the topoisomerase II inhibitor novobiocin were found to disrupt both the in vitro binding of nuclear extracted proteins, from mutant and parental cells, to plasmid DNA and the formation of drug-induced cleavable complexes in vitro. Unexpectedly, Ho33342 induced significant levels of DNA-protein crosslinking in both parental and mutant cells. We conclude that: (i) resistance of the mutant is limited to non-covalently binding minor groove ligands, (ii) Ho33342 can block the trapping of DNA topoisomerase II by enzyme poisons in vitro, (iii) Ho33342 can induce a novel form of DNA-protein cross-link in intact cells, and (iv) the resistance of the mutant is not dependent upon some abnormality in topoisomerase II function.

Amsacrine↗

Antibiotic prophylaxis for the prevention of late infections of prosthetic joints.

Late infection of prosthetic joints as a result of the haematogenous spread of an organism from a remote site with the seeding of that organism on the bone-implanted prosthesis interface is a well-documented but rare complication of prosthetic joint surgery. However, the use of antibiotic prophylaxis is such cases is controversial. The details of 67 previously reported cases of late infection have been reviewed in conjunction with the details of a series of 43 patients, and observations and recommendations regarding antibiotic prophylaxis are made upon the basis of these accumulated data.

Anti-Bacterial Agents↗

A method for determining the cut-off value of a varicella-zoster virus IgG enzyme immunoassay for immune status.

The cut-off optical density (OD) of an enzyme immunoassay (EIA) for IgG antibody to varicella-zoster virus (VZV) was established by application of a statistical technique to OD readings on sera from known susceptible and immune populations. Children aged one to three years who lacked complement fixation (CF) antibody were considered to be known susceptible subjects. Adults whose sera contained antibody by the CF test were considered to be known immune subjects. The method provides a valid alternative to previously used techniques of establishing a cut-off OD, above which reading the EIA can be taken to indicate immunity to varicella-zoster infection.

Antibodies, Viral↗

A comparison of aztreonam and imipenem induction of class I beta-lactamase in Enterobacter cloacae ATCC 13047.

Aztreonam and imipenem were shown to induce Class I beta-lactamase in Enterobacter cloacae ATCC 13047 to a similar extent. Quantitatively, however, aztreonam was far less efficient as an inducer than imipenem. Optimum induction by aztreonam required a concentration of 200 mg/l, which was 800-fold greater than the concentration of 0.25 mg/l of imipenem which resulted in the optimum induction. The differences in the concentrations of aztreonam and imipenem that gave optimum induction were related to the inherent antibacterial activities of the antibiotics when these were determined under the conditions of broth culture. The beta-lactamase activity of sonicated cell samples following induction was inhibited by the presence of aztreonam but not by imipenem. The inhibition was overcome by first washing the cell samples from induced cultures and then incubating the sonicates for a prolonged period at 4 degrees C. It is proposed that the phenomena of an optimum inducing concentration and the interference with the assay of beta-lactamase by the presence of residual antibiotic demonstrated in this study with aztreonam and imipenem would be of relevance when applied more broadly to studies of beta-lactamase induction. In particular these would have a profound effect on the results of studies which attempt to compare the efficacy of beta-lactams as inducers of Class I beta-lactamase.

Aztreonam↗

The penicillins.

The penicillins are among the most useful antibiotics despite the increasing problem of bacterial resistance. The authors review the various penicillins available in Australia and emphasise the rationale for their use and the mechanisms of bacterial resistance to these agents.

Australia↗