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Biomedical subjects

J Munro

Publications and source records attributed to J Munro.

At least 19 recordsLinked to original sources

Twenty-four hour C-peptide and insulin secretion rates and diurnal profiles of glucose, lipids and intermediary metabolites in cirrhosis.

1. To examine the contributions of hypersecretion and decreased insulin clearance to the hyperinsulinaemia of cirrhosis, insulin secretion was calculated over the day from serum C-peptide concentrations and C-peptide metabolic clearance rate. The latter was measured during infusions of recombinant human C-peptide. In cirrhotic patients (n = 9) insulin secretion rate was twice that of normal control subjects (n = 10), both in the basal state [02.00-07.00 hours, 15.7 +/- 2.1 (mean +/- SEM) nmol/h (2.6 +/- 0.4 units/h) versus 7.0 +/- 0.9 nmol/h (1.2 +/- 0.2 units/h), P < 0.002] and over 24 h [787 +/- 93 nmol (132 +/- 16 units) versus 346 +/- 34 nmol (58 +/- 6 units), P < 0.001]. However, the area under the serum insulin concentration curve was approximately six times greater in the cirrhotic patients (24 h basal, 6.3 +/- 1.0 versus 1.1 +/- 0.3 nmol l-1 h, P < 0.001; 24 h total, 21.7 +/- 3.2 versus 3.7 +/- 0.7 nmol l-1 h, P < 0.001). Thus, despite impairment of insulin clearance there is continuing hypersecretion of insulin in cirrhosis. 2. The relationship of carbohydrate and lipid metabolism with insulin secretion was assessed. In cirrhotic patients, 24 h blood glucose profiles showed a worsening of glucose tolerance over breakfast, despite greater insulin secretion compared with other meals, suggesting that the insulin insensitivity of cirrhosis is worse at this time. 3. Cirrhotic patients showed impaired suppression of blood glycerol levels after meals but normal suppression of serum non-esterified fatty acid concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid

Herpes simplex virus encephalitis: problems in diagnosis.

Six children aged 13 days to nine years with herpes simplex encephalitis (HSE) are presented. Institution of appropriate antiviral treatment was later than six days in three cases; original diagnosis in these cases were post-traumatic epilepsy, bacterial meningitis and febrile convulsion. Initially pyrexia was absent in two cases and cranial CT was normal in two cases. Encephalitic changes were observed on the EEGs of five children. Diagnosis was confirmed by paired serological titres, brain biopsy, vesicle culture and CSF titres. The outcome for all six children was poor. HSE should always be considered in children presenting with focal seizures, even when apyrexial and with normal CT findings. In such situations, saving CSF for antibody titres or antigen identification should be routine practice. Treatment with acyclovir is justified before precise virological diagnosis has been established.

Adolescent

Detection of human papillomavirus DNA in skin warts from immunocompromised patients but not in semen from men whose wives have abnormal cervical cytology.

The epidemiology of human papillomaviruses (HPV) was studied in 61 immunocompromised patients (e.g. renal and cardiac transplants; Bowen's disease; genital cancer) undergoing therapy at the University Hospital of Wales at Cardiff U.K. Warts from various sites of these patients were studied for the presence of HPV types 6, 11, 16 and 18 using the dot-blot DNA hybridization technique. Four HPV-16 and one HPV-11 was detected. The presence of HPV-16 in our study is quite significant since it suggests the potential occurrence of genital HPV types in skin warts in immunocompromised patients and hence the need for screening such patients against HPV types. HPV, mainly types 16 and 18 are usually associated with genital cancer, cervical malignancies and cervical intraepithelial neoplasia. The semen of the husband of 30 women with cervical abnormalities and the semen of 30 husbands (control) of wives with normal cervix were tested for HPV-6, 11, 16 and 18. No HPV-DNA could be detected in all of the 60 specimen. This suggests that specimens were either truly negative for any of those types or because virus DNA could present in a small amount less than 5 pg/microliters in some patients. Whether semen plays a role in transmitting HPV is still controversial.

Condylomata Acuminata

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