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Biomedical subjects

J Munro

Publications and source records attributed to J Munro.

At least 91 records · Page 5Linked to original sources

Mutant bias in nonlethal selections results from selective recovery of mutants.

We have characterized a nonlethal selection for mutations that allow Escherichia coli to grow on large maltodextrins (Dex+) in the absence of the lamB encoded maltoporin LamB. These Dex+ mutations occur before and after imposition of the selection and the selection does not result in a general increase in mutagenesis. The recovered Dex+ mutations are almost exclusively mutations that alter the ompF gene that encodes a major E. coli porin, OmpF even though analogous mutations in the homologous ompC gene, which encodes the OmpC porin, can confer a Dex+ phenotype. We show that the bias for ompF mutations results from a biased recovery and that the genetic background of the starting strain and the selection itself influences the type of mutants that are recovered. When we use a strain carrying an amber mutation in the lamB gene we observe the same preference for ompF mutations as when we start with a lamB deletion strain. In addition, we show that there is no preferential mutagenesis of the lamB gene during the selection which induces transcription of the lamB gene. We present evidence that the biased recovery of mutants observed in this selection does not result from adaptive or directed mutagenesis and that the phenotypic fitness which allows recovery of Dex+ mutants involves more than the increased ability to take up maltodextrins.

Bacterial Outer Membrane Proteins↗

Occurrence of faecal bacteria, Salmonella and antigens associated with hepatitis A virus in shellfish.

An investigation was carried out over a one year period to examine jointly the occurrence of faecal bacteria, salmonella and the presence of antigens associated with the hepatitis A virus (HAV) in oysters (Crassostrea gigas), mussels (Mytilus edulis, Mytilus galloprovincialis) and cockles (Cerastoderma edule), taken from 8 shellfish farming areas or natural beds along the French coast. For the faecal coliforms (FC) and faecal streptococci (FS), statistical analysis of the 176 samples examined shows a statistically significant difference between sampling stations (F = 44.39 and F = 26.69 respectively, p less than 0.001): 4 of the 8 stations are more highly contaminated. Salmonella and antigens associated with HAV were detected in 5% and 1.7% respectively of the samples analysed. Frequency of isolation of salmonella is higher for the group of sampling stations where the mean levels of contamination by FC and FS are highest. The presence of HAV associated antigens was detected for the group of stations showing the lowest mean contamination levels. Taking all sample stations together, the percentage of isolation of salmonella differs significantly (chi 2 = 7.28, p less than 0.01) for the two classes of FC established on the basis of the threshold value (300 FC). There is no difference between the two classes of FS. For the HAV-associated antigens, detection percentages are similar for the two classes of results for FC and FS. Within each sampling station, considered independently, no particular correlation was found between the various viral and bacterial markers investigated.

Animals↗

The activity of protein kinases from hamster fibroblasts towards a synthetic peptide based on a carboxy-terminal portion of ribosomal protein S6.

A synthetic decapeptide, S6(231-240), based on a region near the C-terminus of eukaryotic ribosomal protein S6, was used as a substrate for protein kinases (EC 2.7.1.37) from hamster fibroblasts stimulated with fresh medium. Consistent with the results of others using shorter peptides from this region, it was found that the cyclic AMP-dependent protein kinase preferentially phosphorylated the residue corresponding to Ser-235, whereas protein kinase C preferentially phosphorylated the residue corresponding to Ser-236 in this peptide. The peptide did not serve as a substrate for the growth-associated protein kinase from hamster fibroblasts that phosphorylated ribosomal protein S6 in 40S ribosomal subunits, but did serve as a substrate for a previously undetected protein kinase activity that was resolved from the latter by DEAE-cellulose chromatography. This S6(231-240) protein kinase activity did not phosphorylate ribosomal protein S6 in 40S ribosomal subunits, but is possibly a proteolytic fragment of the 40S ribosomal subunit S6 kinase as the latter activity acquired the ability to phosphorylate the decapeptide after partial tryptic proteolysis. The S6(231-240) protein kinase activity preferentially phosphorylated the residue corresponding to Ser-236 with an apparent Km of 15 microM. These results suggest that specific interactions with the ribosome may be required to activate the growth-associated ribosomal protein S6 kinase.

Amino Acid Sequence↗

Rapid diagnosis of oral herpes simplex or zoster virus infections by immunofluorescence: comparison with Tzanck cell preparations and viral culture.

This study compared viral culture with routine cytology and immunofluorescent staining of oral epithelial cell smears for the diagnosis of orofacial infections due to herpes simplex virus (HSV) or herpes zoster (HZ). Twenty-one patients were studied. Viral culture gave the greatest number of positive results, with an assumed sensitivity and specificity of 100%, but the test took at least 24 hours. For haematoxylin and eosin cytology, the corresponding figures for sensitivity and specificity were 54% and 100%, respectively. Direct staining of epithelial smears with FITC-conjugated monoclonal antibodies to HSV type 1, HSV type 2 and HZ had a sensitivity of 82% and specificity of 71%. Smears prepared from oral washings, and stained with the same fluorescent antibodies, yielded a sensitivity of 83% and specificity of 86%. To allow rapid diagnosis, oral epithelial smears for immunofluorescent examination should also be prepared, since in more than 80% of cases such smears will confirm an herpetic infection in less than one hour.

Adult↗

Successful treatment of juvenile chronic arthritis with a specific antiviral agent.

In a previous paper we identified a group of patients with teenage onset chronic progressive arthritis (JCA or JRA) with raised antibody titres to influenza A (H2N2), an epidemic of which was present in the year they were born. On the basis that they might be chronic carriers of influenza A, and that this might be related to their arthropathy, it was decided to use the anti-influenza A drug amantadine to treat the virus and observe whether there was any effect on the joint disease. A 4-month, double-blind, placebo-controlled trial followed by a 4-month open study showed that amantadine could under these circumstances be of considerable therapeutic benefit while having no effect on patients without elevated antibody titres against influenza A.

Adult↗

Antibodies to influenza A in a cluster of children with juvenile chronic arthritis.

In this study of 41 patients with progressive juvenile chronic arthritis (JCA), born between 1946 and 1970, it was noticed that 14 were born in the same year (1963). The possibility of a common environmental factor was therefore investigated. Records showed that an epidemic of influenza A H2N2 was present in that year, and the study shows that JCA patients born in 1963 still have a higher level of antibody to influenza A H2N2 than JCA patients born in other years or age-matched controls. This elevation is not seen in a survey of three control viruses. Since this group developed their clinical JCA after the appearance of influenza A H3N2 in 1977, it is suggested that these patients developed a progressive arthropathy because they had been pre-sensitized to influenza A by contact with an earlier strain when in utero.

Adolescent↗

Hepatitis B in a hospital for the mentally subnormal in South Wales.

The resident population in a long-stay hospital for the mentally handicapped was surveyed in order to assess evidence for past and present infection with the Hepatitis B virus. The authors found a 0.5% prevalence of carriage of Hepatitis Be Antigen and do not recommend mass vaccination of staff and residents in this hospital.

Adult↗

Characterization of a human orphon 28 S ribosomal DNA.

We have isolated clones in which two regions of the human genome are represented, each containing an orphon: a dispersed copy of 28S rDNA. Nucleotide (nt) sequence analysis established that one of these, H28S-O1, corresponds to nt 3627-4105 of human 28S rDNA, but in a mutated form. The orphon was flanked on one side by a portion of the L1Hs long interspersed repeat family of the human genome. Although H25S-O1 is not flanked by the terminal direct repeats characteristic of transposed DNA, it is possible that it is a processed pseudogene.

Base Sequence↗

Urethral syndrome: a self limiting illness.

Thirty nine adult women who were not pregnant and had the urethral syndrome in a general practice underwent detailed microbiological investigations. Patients monitored their own symptoms, and those with persisting symptoms were entered into a randomised controlled trial of treatment with doxycycline and placebo. Chlamydia trachomatis and Neisseria gonorrhoeae were not isolated and fastidious organisms were not causally associated with the urethral syndrome. Treatment with doxycycline showed no benefit; each episode of the urethral syndrome was short and self limiting and there were no recurrences in a median observation period of 12 months.

Adolescent↗

Hyperthermia, Na+K+ATPase and lactic acid production in some human tumour cells.

When HeLa cells are exposed to brief heat shock at 45 degrees C there is a reduction in the cellular level of Na+K+ATPase. Return of the cells to the normal growth temperature of 37 degrees C leads to a partial restoration of enzyme activity. The pattern of this recovery of activity suggests that it may be associated with the induction of heat shock proteins. Indeed other means of heat shock protein induction such as continuous heat treatment at 42 degrees C, or treatment of cells at 37 degrees C with sodium arsenite, leads to elevated levels of Na+K+ATPase activity and alterations in the kinetic properties of the enzyme. Continuous hyperthermia at 42 degrees C led to increased lactate production which could be blocked with ouabain suggesting that effects on Na+K+ATPase activity could partly influence glycolysis. A number of other human and hamster cells also showed increased lactate production at 42 degrees C and also an inhibition of lactate production by ouabain. Whilst incubation of HeLa cells with cyanide had little effect on glycolysis at 37 degrees C elevation of the temperature to 42 degrees C (or 45 degrees C), in the presence of cyanide, impaired glycolysis. The possible role in this phenomenon, of an unusual oxygen-sensitive isoenzyme of lactate dehydrogenase, expressed in human cancers, is discussed.

Animals↗

Preliminary report of an association between measles virus and achalasia.

Complement fixation tests were performed on sera from 18 patients with achalasia and 12 age- and sex-matched controls against a number of bacterial and viral agents in an attempt to ascertain any association with previous infection or any evidence of an altered immune response. There was a statistically significant increase of antibody titre against measles virus in the sera of 21 patients with achalasia compared with age- and sex-matched controls and this was confirmed by haemagglutination inhibition.

Adult↗

Agglutinins to bacteria in Crohn's disease.

Sera from patients with Crohn's disease were tested for antibodies against organisms which are thought to cause inflammatory bowel disease in animals, or have been implicated in human Crohn's disease. Control sera were collected from healthy individuals and patients with ulcerative colitis. Sera from Crohn's disease and controls failed to agglutinate Clostridium colinum or Campylobacter sputorum subsp. mucosalis and two strains of Mycobacterium paratuberculosis (M26 and M27). Most of the sera agglutinated a Citrobacter freundii variant, Mycobacterium paratuberculosis (M28) and Mycobacterium avium (M41) but Crohn's disease sera did not differ from controls. A complement fixation test against Chlamydia gave more positive reactions in patients with Crohn's disease and colitis than in healthy controls. There was a clear difference between the sera from patients with Crohn's disease and other sera, including ulcerative colitis, in agglutination tests with the commensal coccoid rods of the genera Eubacterium and Peptostreptococcus; in these tests 54% of sera from Crohn's disease were positive compared with 11% in ulcerative colitis and none of the sera from healthy controls. All the results were essentially negative with the exception of those from Eubacterium and Peptostreptococcus and these bacteria merit investigation.

Agglutination Tests↗