Search PubMed⌕ Search

Biomedical subjects

S Brewster

Publications and source records attributed to S Brewster.

At least 19 recordsLinked to original sources
PubMed2002

Analysis of minicircle classes in Leishmania (Viannia) species.

This paper reports the analysis of minicircle sequence classes from 4 Leishmania species, all belonging to the 'New World' species of the subgenus Viannia: Leishmania braziliensis, L. guyanensis, L. panamensis and L. peruviana. A minicircle library was constructed for each species, and clones were analysed by restriction enzyme digest and sequence analysis. 319 minicircles from the 4 species were examined and 96 of these were wholly or partially sequenced. The sequences of 41 whole minicircles--21 from L. panamensis, 8 from L. guyanensis and 6 each from L. braziliensis and L. peruviana are presented. Sequence classes were identified within which sequences were highly conserved, with only a small number of single base pair changes between them. In contrast, minicircles from different classes differed significantly, displaying sequence homology only over the minicircle conserved region. Some minicircle classes were identified which were shared between species. These minicircles displayed sequence variation which was potentially species-specific, and were analysed phylogenetically. These results question the hypothesis that minicircle sequence is rapidly evolving and also suggest that an as yet unknown selective pressure maintains sequence class conservation over the entire minicircle molecule even in different species, not only over the conserved region and the guide ribonucleic acid gene. A novel hypothesis is proposed to explain these results.

Animals↗
PubMed2002

A kinetoplast DNA minicircle probe (B18) specific for the Leishmania subgenus Viannia.

This paper reports the development, sequence and specificity of probe B18, which hybridizes only to the kinetoplast deoxyribonucleic acid (kDNA) minicircle of Leishmania species of the subgenus Viannia. This probe was developed in 1985 and has been used extensively since, on whole kDNA, Leishmania dot-blots and kDNA minicircles amplified by the polymerase chain reaction.

Animals↗
PubMed2002

p53 and bcl-2 immunohistochemistry in preoperative biopsies as predictors of biochemical recurrence after radical prostatectomy.

OBJECTIVE: To evaluate p53 and bcl-2 immunohistochemistry in preoperative biopsies and radical prostatectomy specimens, as predictors of biochemical recurrence. PATIENTS AND METHODS: Preoperative biopsies from 73 men, and the radical prostatectomies from these men and from a further 47 men, were evaluated. The serum prostate specific antigen (PSA) level, Gleason score, pathological stage and margin involvement were recorded. The immunohistochemical expression of p53 and bcl-2 was studied on a representative area of tumour with the highest Gleason grade. The median follow-up was 53 months. RESULTS: During the follow-up 47 of the 120 patients had a biochemical recurrence. Capsular penetration was present in 63 (53%) and the surgical margins were positive in 47 (39%). The Gleason score was < 7 in 81 (68%) patients; p53 was positive in 40 (66%) of 61 biopsies and 84 (71%) of 118 prostatectomy specimens. Bcl-2 was positive in eight (13%) of 63 biopsies and 20 (17%) of 118 prostatectomies. On multivariate analysis the biopsy p53, Gleason score and serum PSA were significant predictors of recurrence. On multivariate analysis, capsular penetration, PSA and margin status at prostatectomy were significant predictors of recurrence. There was also a significant interaction between PSA and margin status. Although univariately significant, neither p53 nor bcl-2 featured in the final multivariate model. CONCLUSION: Biopsy p53 status significantly predicts recurrence after radical prostatectomy, but its low specificity and technical issues suggest that it will not be useful in the clinical setting. However, a patient with negative p53 on biopsy is likely to have a good prognosis on prolonged follow-up.

Aged↗
PubMed2000

Comparison of the frequency of behavioral disinhibition on alprazolam, clonazepam, or no benzodiazepine in hospitalized psychiatric patients.

Several case reports have suggested that treatment with the benzodiazepine alprazolam can result in behavioral disinhibition. To address this question, the authors reviewed the medical records (blinded to all pharmacologic treatments the patients received) of 323 psychiatric inpatients treated with alprazolam (108 patients), clonazepam (111 patients), or no benzodiazepine (104 patients) between January 1989 and June 1990. During benzodiazepine treatment, there were no significant differences among the three groups on the following measures: (1) acts of self-injury (alprazolam, 1.9%; clonazepam, 1.8%; no benzodiazepine, 2.9%); (2) assaults on staff or other patients (alprazolam, 0%; clonazepam, 0.9%; no benzodiazepine, 1.0%); (3) need for seclusion or restraints (alprazolam, 3.7%; clonazepam, 6.3%; no benzodiazepine, 4.8%); (4) increased need for observation by hospital staff (alprazolam, 8.3%; clonazepam, 7.2%; no benzodiazepine, 6.7%); and (5) decrease in patient privileges (alprazolam, 11.1%; clonazepam, 12.6%; no benzodiazepine, 11.5%). The results indicate that in an inpatient psychiatric population, the frequency of behavioral disturbances with alprazolam, clonazepam, or no benzodiazepine does not differ. This suggests that alprazolam does not possess unique disinhibitory activity. Second, these data suggest that disinhibition may not be an important clinical problem associated with benzodiazepine use. The design of the study does not allow one to establish a relationship between the prescription of the benzodiazepine and worsening behaviors, and the findings need to be interpreted conservatively because it was a retrospective review of a heterogeneous population. However, it is noteworthy that the incidence of adverse events was low even in this high-risk population, and because the patients were in the hospital and under constant observation, the objective assessment of so-called paradoxical reactions was undertaken in a controlled setting.

Adolescent↗
PubMed1999

Polymerase chain reaction-based identification of New World Leishmania species complexes by specific kDNA probes.

Here we define a new approach for the detection and characterisation of Leishmania complexes by polymerase chain reaction (PCR) and specific hybridisation. The first step consists of PCR amplification of kDNA minicircles using general kinetoplastid primers, which generate a polymorphic multi-banding pattern for all Leishmania species and other Kinetoplastidae. The second step is the identification of the Leishmania species complexes by hybridisation of the PCR products with specific kDNA probes. Polymorphic PCR-products from a genetically diverse set of Leishmania species were analysed by electrophoresis and the banding patterns compared with multi-locus enzyme electrophoresis (MLEE) data. The banding patterns produced by Leishmania species were very heterogeneous, making kDNA-PCR useful for determining closely related strains and for fingerprinting individual strains. The degree of kDNA-PCR and MLEE polymorphism was compared using UPGMA dendrograms. Three complex-specific probes were generated from major PCR bands of reference stocks belonging to the Leishmania mexicana, Leishmania donovani and Leishmania braziliensis complexes, and hybridisation of these probes to membrane-bound PCR products could reliably identify the strain to a complex level. A combination of kDNA-PCR fingerprinting and hybridisation with kDNA probes was found to be useful for both sensitive detection and direct identification of Leishmania species complexes.

Animals↗
PubMed1999

Intra and inter-specific microsatellite variation in the Leishmania subgenus Viannia.

Leishmania species of the subgenus Viannia are responsible for a large proportion of New World leishmaniasis. Here we report the development of a set of microsatellite markers which are able to discriminate between all species within the subgenus Viannia, including the closely related species pairs: Leishmania (V.) braziliensis and Leishmania (V.) peruviana; Leishmania (V.) panamensis and Leishmania (V.) guyanensis. Potential species hybrids were uncovered in the analysis. These markers are sufficiently polymorphic such that within-species epidemiological, population and genetic studies are theoretically possible for all species analyzed.

Animals↗
PubMed1999

The ATPase subunit 6 gene sequence predicts that RNA editing is conserved between lizard- and human-infecting Leishmania.

Here we investigate the similarities in the kinetoplastid RNA editing process between human- and lizard-infecting Leishmania species. We present the sequence of the maxicircle-encoded ATPase subunit 6 gene from L. (V.) panamensis, L. (L.) mexicana and L. (L.) donovani species of human-infecting Leishmania. These represent the first available sequences of this gene from Leishmania species other than the lizard-infecting L. tarentolae. The gene sequences are highly conserved, both over the edited and unedited parts of the gene, implying that the RNA editing process is likely to be highly conserved between Leishmania species. Indeed, the first editing domain is absolutely conserved in all three Leishmania species studied and L. tarentolae. A phylogeny based on part of the ATPase subunit 6 gene placed the lizard-infecting Leishmania within the monophyletic Leishmania genus, supporting previous data which suggest that lizard- and human-infecting Leishmania species are closely related.

Adenosine Triphosphatases↗
PubMed1998

Analysis of the genomic organisation of a small chromosome of Leishmania braziliensis M2903 reveals two genes encoding GTP-binding proteins, one of which belongs to a new G-protein family and is an antigen.

Leishmania braziliensis M2903 contains a highly amplified small chromosome. This work is aimed at resolving its structural organization and determining whether this unusual chromosome contains specific genes encoding proteins with important functions in disease pathology or drug resistance. Our results show that the M2903 250-kb small chromosome contains LD1 sequences and has an inverted repeat structure. The LD1 sequences and two cDNAs (cDNA2 and cDNA53) were mapped on a cosmid contig, and the two cDNAs and the corresponding genomic fragments from the small chromosome were sequenced. The gene encoding cDNA2 predicts a putative GTP-binding protein with homology to other GTP-binding proteins only in the G-1 domain region; however, four other conserved motifs can be recognized. Sequence similarity to cDNA53 is located in at least five chromosomes, and its small chromosome copy is a pseudogene. An open reading frame downstream of the cDNA53 pseudogene predicts another GTP-binding protein that belongs to a new G-protein family with an unusual conserved GTP-binding domain and a newly characterized conserved sequence motif. A portion of this GTP-binding protein gene was studied previously in L. aethiopica as a recombinant antigen that reacts with human antibodies.

Amino Acid Sequence↗
PubMed1997

Genomic DNA repeat from Leishmania (Viannia) braziliensis (Venezuelan strain) containing simple repeats and microsatellites.

In this paper the Leishmania (Viannia) braziliensis complex is defined as containing all species of the actual subgenus Viannia. Organisms of the L. (V) braziliensis complex are the causative agents of localized human cutaneous and mucocutaneous leishmaniasis in South America, much of Central America and some ares of North America. In our search for better species and subspecies diagnostic probes we focused our research on repetitive DNA, since it provides a greater number of target sites for hybridization. In this work we report the isolation and sequencing of a 1.8 kb DNA region, LbJ38, which is probably tandemly repeated or dispersed at least 4 times along one chromosome and is naturally present in L. (V) braziliensis genomic DNA. This region contains microsatellites and simple repeat DNA sequences and was isolated by screening a genomic DNA cosmid library with complex- and species-specific probes. No homology was found with other Leishmania microsatellite or repetitive DNA. The utility of this repetitive sequence and primers derived from it in the identification of L. (V) braziliensis is demonstrated. As far as we are aware, this is the first report of sequence characterized repetitive microsatellite and GC rich simple repeat DNA from the nuclear genome of New World Leishmania.

Animals↗
PubMed1996

Problems in diagnosis and management of goitre in childhood and adolescence.

This study is a retrospective review of 17 patients aged 16 and under with a total of 18 goitres, who were investigated and treated at Bristol Children's Hospital and Bristol Royal Infirmary between 1967 and 1994. There were five neoplasms, comprising follicular adenoma (three) and papillary carcinoma (two). Other benign causes of goitre included nodular goitre (four), non-toxic hyperplasia (three) and chronic lymphocytic thyroiditis (three). The authors suggest some guidelines to help in the diagnosis and management of goitre in young patients, as a consequence of significant difficulties encountered in 12 of the 17 patients in this series.

Adenoma↗
PubMed1993

A new polymorphic marker (D10S97) tightly linked to the multiple endocrine neoplasia type 2A (MEN2A) locus.

Familial multiple endocrine neoplasia type 2A (MEN 2A) is a cancer syndrome that is inherited as an autosomal dominant with high penetrance. Its clinical features are medullary carcinoma of the thyroid, pheochromocytomas, and hyperparathyroidism. A new polymorphic locus D10S97 (probe: KW6 delta SacI) detects a codominant EcoRI polymorphism that is tightly linked to the MEN2A locus. The peak lod score for linkage between D10S97 with MEN2A is 13.03 at theta = 0.00. The polymorphic locus D10S97 maps, by linkage analysis, into the previously defined interval between FNRB and RBP3 to which MEN2A has been assigned. We present physical mapping data showing that the probe pKW6 originates from 10p13 and that the polymorphic locus D10S97 in 10q11.2 is detected by cross-hybridization.

Animals↗
PubMed1991

Can knee replacements be assessed by post?

The audit of knee replacement surgery requires long-term follow-up. The aim of this Bristol study was to examine whether an accurate assessment of knee replacement surgery could be undertaken by post, thus obviating the need for patients to visit hospital. A patient's questionnaire was designed to complement the clinic therapist's assessment form currently in use, and this was completed by 73 patients without supervision prior to the therapist's assessment. A comparison of the two assessments shows a significant discrepancy between their results, particularly in the assessment of pain, walking distance, and range of movement. The authors conclude that postal follow-up of knee replacements should be viewed with caution.

England↗