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Biomedical subjects

A Brown

Publications and source records attributed to A Brown.

At least 433 records · Page 24Linked to original sources

The biosynthetic implications of acetate and glutamate incorporation into (3R,5R)-carbapenam-3-carboxylic acid and (5R)-carbapen-2-em-3-carboxylic acid by Serratia sp.

Two new beta-lactams have been isolated from strains of Serratia and Erwinia sp. and identified as (3R,5R)- and (3S,5R)-carbapenam-3-carboxylic acid. These novel carbapenams lack antibacterial activity, are resistant to both beta-lactamases I and II from Bacillus cereus and are not detected by the lactamase induction assay. Radiolabelled and stable isotope experiments have established that both metabolites together with the antibiotic 5R-carbapenem-3-carboxylic acid are glutamate and acetate derived. A number of possible pathways for the biosynthesis of these compounds as well as their relationship to the more complex members of the carbapenem family of beta-lactam antibiotics are discussed.

Acetates↗

A method for the isolation and culture of human colonic crypts in collagen gels.

Little is known concerning the biological factors that control the proliferation of the stem cells of the colonic mucosa. In part this is due to a lack of systems suitable for studying the proliferation of this mucosa in vitro. We describe a simple technique for the isolation of single viable intact crypts which are free of stroma and which can then be cultured for periods of at least 16 d using a collagen gel culture method. This method of crypt isolation was efficient with the mean yield of viable intact crypts being 1.4 +/- 1.2 X 10(4) (mean +/- 1 SD) crypts/cm2 of mucosa. In culture, mucosal cells only survived for extended periods when the crypts were cultured in collagen gels over a feeder layer of bovine aortic endothelial cells. Cells containing mucus were present in the cultured crypts at all stages of the culture; however we have not been able to demonstrate alkaline phosphatase activity in these crypts. Studies of DNA synthesis after 7 d in culture, using a 18-h pulse label with bromodeoxyuridine (BUdR) has shown that DNA synthesis, as measured by incorporation of BUdR into nuclei, is still occurring in these cultured crypts.

Cell Separation↗

Mutagenic activity of fluorides in mouse lymphoma cells.

The L5178Y mouse lymphoma cell forward-mutation assay was used to test for the mutagenic activity of sodium and potassium fluoride at the thymidine kinase locus. Mutants were detected by colony formation in soft agar in the presence of trifluorothymidine. Mutagenic and toxic responses were observed in the concentration range of 300-600 micrograms/ml with both sodium and potassium fluoride. Approximately 3-fold increases in mutant frequency were observed for concentrations in the 500-700 micrograms/ml range that reduced the relative total growth to approximately 10% in the absence or presence of a rat-liver S9 activation system. A sample of 30% sodium fluoride-70% sodium bifluoride (NaHF2) induced a similar mutagenic response but was more toxic with respect to the fluoride concentration. A specificity for fluoride ions in causing mutagenesis was indicated by the fast that much higher concentrations of sodium or potassium chloride were necessary to cause toxicity and increases in the mutant frequency. The possible involvement of chromosomal changes was signaled by the predominant increase in the small colony class of mutants.

Animals↗

Low dose low osmolar intravenous urography.

A prospective double blind randomised trial using 25 ml of Hexabrix 320 (ioxaglate, May and Baker), Niopam 370 (iopamidol, Merck) or Omnipaque 350 (iohexol, Nycomed) intravenous urography was carried out. The results showed no perceptible difference in the diagnostic quality of urograms with each of the media. An additional 25 ml of contrast medium was required by 4% of patients in order to obtain a satisfactory examination. We recommend that a dose of 25 ml of low-osmolar medium be used for all patients with the exception of the obese, those taking diuretics or those who have renal impairment.

Adolescent↗

An attenuated aroA Salmonella typhimurium vaccine elicits humoral and cellular immunity to cloned beta-galactosidase in mice.

beta-Galactosidase (GZ) is an intracellular protein that is frequently used to express cloned antigens as fusion proteins in Escherichia coli. Salmonella typhimurium strain SL3261, an attenuated aroA vaccine strain, was used as a carrier for the plasmid pXY411, which directs the expression of GZ in salmonellae (which do not normally produce this protein). The resulting strain--SL3261(pXY411)--expressed GZ as an intracellular antigen. The plasmid was stable in vitro and in vivo and did not significantly alter the behavior of strain SL3261 in mice. Animals intravenously vaccinated with this construct developed circulating antibodies to GZ, as measured by ELISA, and delayed hypersensitivity to the antigen injected in the footpad. These results indicate that attenuated salmonellae may be expected to elicit both humoral and cellular responses to intracellular cloned antigens.

Animals↗

Cell surface hydrophobicity and charge of Staphylococcus aureus and coagulase-negative staphylococci from bovine mastitis.

The effects of seven growth media on cell surface hydrophobicity of a collection of Staphylococcus aureus and coagulase-negative staphylococci isolated from bovine mastitis were compared in the salt-aggregation test. Thirty-three per cent of Staph. aureus strains showed extremely high cell surface hydrophobicity (auto-aggregated) and 28% were moderately hydrophobic while 26% were hydrophilic after growth on horse blood agar at 37 degrees C for 18 h. There were great variations in the proportion and degree of the hydrophobicity depending on the medium used. Cultivations on/in capsule-inducing media caused a shift from a high to a low degree of hydrophobicity, although a microscopically detectable capsule or slime layer was seen in only one strain. This strain and encapsulated reference strains had a hydrophilic cell surface and migrated faster in free zone electrophoresis than cells of unencapsulated strains. Cells of strains grown on staphylococcus medium 110 agar migrated faster than those grown on horse blood agar regardless of their capsule production. Coagulase-negative staphylococci showed uniformly hydrophilic cell surface after cultivation on horse blood agar, but not when grown in tryptic soy broth or proteose peptone broth. It was concluded that most of the Staph. aureus strains from bovine mastitis under a variety of growth conditions in stationary phase culture constantly expressed hydrophobic cell surface.

Animals↗

Diversity of plasmids in Achromobacter xylosoxidans isolates responsible for a seemingly common-source nosocomial outbreak.

Achromobacter xylosoxidans, an uncommon yet highly resistant opportunistic pathogen, was isolated from nine hospitalized patients during an 8-month period. It had been isolated from only seven patients with either nonfatal infection or colonization from 1981 to 1984. From June 1985 to January 1986, A. xylosoxidans was isolated 18 times from seven different sites (sputum, 7 times; urine, 4 times; blood, 3 times; and lung, pleural fluid, wound tissue, and tracheal aspirate, 1 time each). Four patients died, including the three with bacteremia. All but two patients had nosocomial infections and either were on the same ward or were cared for by the same staff members. Eleven A. xylosoxidans strains yielded eight distinct plasmids (8, 21, 23, 26, 38, 50, 51, and 64 megadaltons). Whole-cell peptide patterns of 10 of these strains were determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Isolates from the same patient contained the same plasmids and had identical peptide patterns but differed from other strains in both parameters. Plasmids were absent from the two community-acquired isolates. Although nosocomial strains showed similar antibiotic resistance patterns (only moxalactam and ticarcillin-clavulanic acid were uniformly active) and cross-contamination was strongly suggested epidemiologically, results of plasmid and peptide analyses did not support the possibility of a single-strain outbreak.

Adult↗

Further assessment of the effects of occupational radiation exposure in the United Kingdom Atomic Energy Authority mortality study.

The United Kingdom Atomic Energy Authority mortality study was designed to investigate the relation between exposure to ionising radiation and mortality among the authority's employees. The present paper describes some of the problems encountered in assessing occupational exposure to low dose radiation and examines whether the study's conclusions about the relation between exposure and mortality could be affected by the methods used. The study covered the years 1946 to 1979 during which time the frequency with which personal film dosimeters were issued changed from weekly to monthly, and the threshold level below which measurements were not made decreased 20-fold. Exposure from "below threshold" readings made an important contribution to total exposure in the early years. Estimates, based on the remeasurement of a sample of old films, indicated that the average whole body exposure before 1961 may have been about double that which was measured. Furthermore, although records were kept of when dosimeters were lost or damaged, the associated exposures were unknown and could only be estimated. Workers whose dosimeter readings were missing for more than 5% of the time during which they were monitored had higher all cause mortality (p = 0.04) and higher mortality from accidents and violence (p = 0.05) than other radiation workers. The results of analyses of mortality in relation to whole body exposure were compared when the exposures included estimates of the below threshold and missing exposures and when these exposures were assumed to be zero. Some of the findings differed, but none changed sufficiently to alter the general conclusions. Although the trend in mortality from all cancers changed from one in which the increase with exposure was far from statistically significant (p = 0.3) when the below threshold and missing values were assumed to be zero to one that approached significance (p = 0.06) after they were estimated, calculations of the annual excess deaths from cancer per unit dose resulted in broadly similar estimates. Studies of workers exposed to ionising radiation usually focus on mortality in relation to whole body exposure. In the present paper its relation to neutron and surface exposure is also examined. Workers with measured neutron exposures had significantly lower all cause mortality than other workers with a radiation record (p = 0.03). Surface exposure was significantly related to mortality from all cancers (p = 0.02) and prostatic cancer (p less than 0.001). Some data on cancer registration are presented but these cannot be readily interpreted because cancer registration details were available only for ex-employees who may not be typical of the workforce as a whole.

Humans↗

Transient neutropenia of childhood.

Patient characteristics and clinical course are described in 21 children with newly discovered neutropenia (absolute neutrophil count less than 1500/microliter). Only children over age 3 months are included; 19 of 21 were less than age 2 years. The majority had respiratory tract infections and 11 had been on various medications at the time neutropenia was discovered. Bacteria were isolated from the blood of three patients (S. pneumoniae in two, H. influenzae in one) and from urine in one (E. coli). Respiratory syncytial virus was cultured from the nasopharynx of two patients. Opportunistic, gram-negative and staphylococcal infections did not occur. Neutrophil counts in all but one child returned to normal within 6 weeks of onset; half recovered within 7 days. Bone marrow examination was performed in 13 patients: maturation arrest at various stages in the myeloid series was noted in six, and seven had normal myeloid maturation. Bone marrow findings did not correlate with degree or duration of neutropenia. These observations indicate that previously well infants with isolated neutropenia generally have a benign clinical course, although three patients were ultimately proven to have significant chronic illness. Recommendations are made as to management.

Agranulocytosis↗

The impact of a liaison psychiatry service on patterns of referral in a general hospital.

A retrospective study of psychiatric referrals from a general hospital inpatient population was carried out for three separate years, 1973, 1976 and 1979. Reorganisation of the liaison service to the responsibility of one consultant team was associated with changes in referral rate and disposal. In particular, there was a significant increase in the referral rate of patients from medical and surgical wards who were not involved in acts of deliberate self-harm.

Hospitals, General↗