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Biomedical subjects

H Vaughan

Publications and source records attributed to H Vaughan.

At least 19 recordsLinked to original sources

External quality assessment for detection of Chlamydia trachomatis.

The use of molecular methods for detection of Chlamydia trachomatis is increasing in clinical laboratories. External quality assessment enables unbiased monitoring of the performance of laboratories in the detection of specific pathogens. This study details the results of molecular and enzyme immunosorbent assay (EIA) testing for C. trachomatis detection in simulated endocervical swab specimens recently distributed internationally by United Kingdom National External Quality Assessment Scheme for Microbiology (UK NEQAS for Microbiology) external quality assessment panels. The frequency of accurate detection of C. trachomatis in the panels ranged from 32 to 100%. Participants using molecular methods were significantly more likely to detect C. trachomatis in specimens than those using an EIA. Two strains were distributed with the panels: an L2 laboratory-adapted strain and an uncharacterized primary isolate. Further analysis indicated a difference in detection of C. trachomatis between specific methods only with the L2 strain at lower concentrations. In addition, eight negative specimens were distributed, and false positives were found to be rare by all methods included in the study.

Chlamydia trachomatis↗

Dengue viruses in the Caribbean. Twenty years of dengue virus isolates from the Caribbean Epidemiology Centre.

The first isolate of a dengue virus in the Americas was obtained in Trinidad and Tobago in 1953, and several dengue virus isolates were obtained in subsequent years. However, the systematic isolation and typing of dengue viruses in support of virus surveillance and outbreak investigations did not start until the creation of the Caribbean Epidemiology Centre (CAREC) in 1975. Since then, over two thousand viral isolates have been obtained and typed from many countries in the English and Dutch-speaking Caribbean. In this communication, virological data from 17 countries between 1977 and 1996 are presented and analyzed together for the first time with available epidemiological data. Types 1, 2 and 4 were isolated over the period, and geographic and temporal patterns in the distribution of the most prevalent strains are presented. The historical surveillance data is critically assessed. A temporal correlation with reported dengue incidence and rainfall data in Trinidad and Tobago is reported. Recent changes in epidemiological patterns are described, including reference to two large later outbreaks. Risk assessment of complicated forms of dengue virus infections in the Caribbean has been attempted, with some success. The importance of ongoing systematic surveillance is discussed.

Age Distribution↗

Expression of the MAGE-1 gene in human hepatocellular carcinomas.

OBJECTIVE: To further investigate the expression of MAGE-1 gene in hepatocellular carcinoma (HCC). METHODS: The tumors and adjacent liver tissue from 45 HCC patients and liver tissue from 28 non-HCC patients (16 with liver cirrhosis and 12 with normal liver) were characterized by RT-PCR. A 421 bp PCR product from a cDNA fragment spanning exons 1, 2 and 3 was sequenced. The HLA type was assayed by standard ELISA in 43 HCC patients. RESULTS: Thirty-two of 45 tumor tissues from HCC patients expressed MAGE-1 mRNA (71.1%). In contrast, MAGE-1 mRNA was not detected in adjacent tissues. Three were found to have point mutations at 3 identical sites resulting in the substitution of two amino acid residues. The most frequent HLA types in 43 HCC patients were: HLA-A2, 53.5%; A11, 25.6%; A24, 20.9%; A33, 20.9%; HLA-B13, 28.3% and B35, 23.2%. Expression of HLA-A33 (20.9%) was higher in HCC patients than that predicted in the normal Chinese population (8.8%). There was no discemable correlation between MAGE-1 expression and alpha-FP level, tumor size and hepatitis B or C virus infection. The identification of peptides which are restricted by haploptypes other than A1 should increase the opportunity for peptide based immunotherapy. CONCLUSIONS: This study shows that MAGE-1 mRNA is highly expressed in HCC tumor tissue in Chinese patients. Previously unreported point mutations in the MAGE-1 gene are described and may also provide additional opportunities for immunotherapy.

Amino Acid Sequence↗

Antibody and T cell responses of patients with adenocarcinoma immunized with mannan-MUC1 fusion protein.

Mucin 1 (MUC1) is a large complex glycoprotein that is highly expressed in breast cancer, and as such could be a target for immunotherapy. In mice, human MUC1 is highly immunogenic, particularly when conjugated to mannan, where a high frequency of CD8(+) MHC-restricted cytotoxic T lymphocytes is induced, accompanied by tumor protection. On this basis, a clinical trial was performed in which 25 patients with advanced metastatic carcinoma of breast, colon, stomach, or rectum received mannan-MUC1 in increasing doses. After 4 to 8 injections, large amounts of IgG1 anti-MUC1 antibodies were produced in 13 out of 25 patients (with antibody titers by ELISA of 1/320-1/20,480). Most of the antibodies reacted to the epitopes STAPPAHG and PAPGSTAP. In addition, T cell proliferation was found in 4 out of 15 patients, and CTL responses were seen in 2 out of 10 patients. Mannan-MUC1 can immunize patients, particularly for antibody formation, and to a lesser extent, cellular responses. It remains to be seen whether such responses have antitumor activity.

Adenocarcinoma↗

Molecular characterisation of the gene for the 180 kDa subunit of the DNA polymerase-primase of Drosophila melanogaster.

We have cloned and sequenced the gene for the 180 kDa subunit of the a polymerase from Drosophila melanogaster. The protein shows high similarity to the 180 kDa subunits from other species. Comparative expression analysis for the transcript, protein and enzymic activity suggests that control occurs mainly at the level of transcription. In situ analyses of the RNA suggest that high levels of the transcript are synthesised in the ovaries and deposited uniformly in the egg. Immunolocalisation of the 180 kDa polypeptide in whole embryos shows that its location is mainly nuclear; however, dispersal of the protein can be seen to occur during mitotic phases of the cell cycle.

Amino Acid Sequence↗

Auditory event-related potentials in children at risk for schizophrenia: the complete initial sample.

Event-related potentials (ERPs) were recorded from children of schizophrenic parents, children of parents with affective disorders, and children of parents without a history of psychiatric illness. ERPs were elicited during a modification of the "oddball" paradigm, in which two infrequents (a change in pitch and a missing stimulus) were embedded in a series of frequent background events. The data were recorded from electrodes located at midline frontal, central, parietal, and occipital scalp sites. Diagnostic assessments of the parents were performed using the Schedule for Affective Disorders and Schizophrenia-Lifetime Version (SADS-L) and Research Diagnostic Criteria (RDC). Behavioral assessments of the children were made with a modified version (BGAS) of the Global Assessment Scale. ERP amplitudes for several electrophysiological events were compared among groups for target and nontarget stimuli using analyses of of variance of both factor score and baseline to peak measures. No systematic differences suggesting waveform abnormalities in the children of schizophrenic parents (high-risk subjects) were found. However, when the results were analyzed using only those children whose parents had a "pure" diagnosis of either schizophrenia or affective disorder, the children of affectively disordered parents (psychiatric control subjects) showed significantly lower N100 amplitudes (to the frequent event only) than either the normal control or high-risk subjects. No consistent behavioral differences among the three groups emerged. Since only a small percentage of children at risk will eventually develop schizophrenia, ERP amplitude frequency distribution analyses were also performed and compared among groups. However, these did not provide evidence of an outlying subgroup in any of the three groups. There were complex relationships between ERP component amplitudes and behavioral adjustment in adolescence but, in general, these did not distinguish high-risk and psychiatric control subjects from each other. There was no evidence of a relationship between deviant attentional functioning as measured in an earlier round of laboratory testing and ERP late component amplitude.

Adolescent↗

Event-related potentials in children at risk for schizophrenia during two versions of the continuous performance test.

Event-related potentials (ERPs) were recorded from children of schizophrenic parents, children of parents with affective disorders, and children of parents without a history of psychiatric illness. ERPs were elicited during two versions of the continuous performance test (CPT), which differed in their level of processing complexity. The data were recorded from electrodes located at midline frontal, central, parietal, and occipital scalp sites. Diagnostic assessments of the parents were performed using the Schedule for Affective Disorders and Schizophrenia-Lifetime Version and Research Diagnostic Criteria. Clinical assessments of the children were made with a modified version of the Global Assessment Scale. ERP amplitudes for six electrophysiological events were compared among groups for target and nontarget stimuli using analyses of variance of both factor score and baseline to peak measures. There was one isolated between-group finding: frontal negative slow wave recorded at FZ was of greater magnitude in the high risk (HR) than in either the psychiatric (PC) or normal control (NC) groups. Since only a small percentage of children at risk will eventually develop schizophrenia, ERP amplitude deviance and frequency distribution analyses were also performed and compared among groups. ERP component amplitudes did not distinguish the groups when each component was considered separately. Deviance analyses, using a combination of the amplitudes of the six ERP components, also did not provide evidence of a deviant subgroup within any of the three groups. There appeared to be no relationship between ERP component amplitudes and behavioral adjustment in adolescence. Some evidence of a relationship between deviant attentional functioning and ERP component amplitude was found, but the pattern of findings within the attentionally deviant HR subgroup was opposite to that found for the HR group as a whole and more consistent with the pattern found for the NC group.

Adolescent↗

Histocompatibility antigens (HLA): associations with immunopathic diseases and with responses to microbial antigens.

Described is the experience from a single histocompatibility typing laboratory sampling, firstly, Australian patients with various immunopathic diseases and, secondly, subjects previously classified as "responders" or "non-responders" to various microbial antigens. The diseases considered included chronic active hepatitis (CAH) and various cirrhoses, "thyrogastric" autoimmune diseases, systemic lupus erythematosus (SLE), rheumatoid arthritis, dermatitis herpetiformis (DH) with intestinal villous atrophy, and multiple sclerosis (MS). The immune responses considered included those to flagellin, candidin, mumps, trichophyton, tuberculin and streptococcal enzymes. The HLA specificities particularly associated with disease included B8 (CAH, thyrotoxicosis SLE, DH, and miscellaneous immunopathic diseases) and B7 (thyrotoxicosis, SLE, DH, and MS). The same specificities were present in excess, although not impressively so, among responders to certain of the microbial antigens, i.e. B7 with high responders to flagellin and B8 (and A1) with responders to trichophyton.

Adult↗

Pancreatic islet-cell antibodies in diabetes mellitus correlated with the duration and type of diabetes, coexistent autoimmune disease, and HLA type.

In a study of 972 patients with diabetes mellitus, humoral pancreatic islet-cell antibodies (I.C.Ab.) were detected in highest prevalence in insulin-treated diabetics with (38 per cent) and without (22 per cent) associated overt organ-specific autoimmune disease (A.I.D.) where consideration was not given to the duration of diabetes. They were also detected in 8 per cent of diabetics treated with oral hypoglycemic agents (O.H.A.), but not in diabetics requiring diet alone and in only 0.5 per cent of 434 control subjects. Six per cent of 522 patients with overt organ-specific A.I.D. but not diagnosed to be diabetic had I.C.Ab.s. I.C.Ab.s were present in the sera of 2 per cent of 157 first-degree relatives of I.C.Ab.-positive subjects. In insulin-treated diabetics and, to a lesser extent, in diabetics not requiring insulin, the prevalence of humoral I.C.Ab. was strongly dependent of the duration of the diabetes, being 60 per cent during the first year from diagnosis in the insulin-treated group and falling to 20 per cent at two to five years and to 5 per cent at 10-20 years. The prevalence of I.C.Ab. in insulin-treated diabetics showed no correlation with the patient's age at the time of testing when the duration of diabetes was taken into account. Diabetics who did not require insulin for treatment but who were I.C.Ab.-positive showed a significant tendency to subsequently require insulin and to have a higher prevalence of other autoantibodies than insulin-independent diabetics who were I.C.Ab.-negative. Persistence of I.C.Ab. for more than five years from diagnosis of diabetes was associated with coexistent overt organ-specific A.I.D. and with HLA-B8, A1, and A1 + B8.

Adult↗

HLA in asthma.

100 adult patients with asthma were typed for HLA. These patients were skin tested with a panel of allergens and divided into skin test positive (61) and skin test negative (39) patients. There was a decreased frequency of HLA-B12 in the negative skin test group (18%) compared to the skin test positive group (43%) and the controls (36%). A further subdivision of these patients into extrinsic asthma (positive skin tests and/or allergic history) and intrinsic asthma (negative skin tests and no allergic history) was made. There was an increased frequency in the extrinsic asthmatics of HLA-B8 (37 compared to 28% in normals) and a decreased frequency of B12 in the intrinsic asthmatics (13 compared to 36% in normals). 4 or 5 patients who had negative skin tests but gave a history of asthma following exposure to specific allergens, suggesting a type III immune complex asthma, were both A1 and B8.

Adolescent↗

HLA and pancreatic islet cell antibodies in diabetes.

The frequency of HLA-B8 was significantly increased in pancreatic islet cell antibody (P.I.C.A)-positive patients (61%) compared with P.I.C.A.-negative patients (35%) and a control population (28%). This increased frequency of HLA-B8 was even more striking in diabetics in whom P.I.C.A. persisted for more than 5 years (71%). Thus the association of HLA-B8 with diabetes may be related to the presence of P.I.C.A. in these patients.

Adolescent↗

The effects of calcium ions on the activities of trehalase, hexokinase, phosphofructokinase, fructose diphosphatase and pyruvate kinase from various muscles.

1. The effects of Ca(2+) on the activities and regulatory properties of trehalase, hexokinase, phosphofructokinase, fructose diphosphatase and pyruvate kinase from vertebrate red and white muscle and insect fibrillar and non-fibrillar muscle have been investigated. These muscles were selected because of the possible difference in the role of glycolysis in energy production in the vertebrate muscles, and the possible difference in the role of Ca(2+) in the control of contraction in the two types of insect muscle. An increase in Ca(2+) concentration from 0.001mum to 10mum did not modify the activities nor did it modify the regulatory properties of these enzymes from these various muscles. 2. Concentrations of Ca(2+) above 0.1mm inhibited the activities of hexokinase and phosphofructokinase from the different muscles. It has been suggested that this inhibition may provide the basis for a theory of regulation of glycolysis (Margreth et al., 1967). If phosphofructokinase is located within the sarcoplasmic reticulum, its activity will be inhibited when the muscle is at rest, but the release of Ca(2+) from the reticulum during contraction will lead to a stimulation of its activity and hence an increase in glycolytic flux. The distribution of hexokinase and phosphofructokinase in the various cell fractions of these muscles was very variable. In particular, both enzymes were present almost exclusively in the 100000g supernatant fraction in the extracts of insect flight muscles. Thus there is no correlation between the properties of the enzymes and their distribution in muscle. 3. It is concluded that Ca(2+) does not control the activities of the important regulatory enzymes of glycolysis in muscle. It is suggested that in some muscles the sensitivity of the control mechanism at the level of phosphofructokinase to changes in the concentration of AMP may be increased by a process known as ;substrate-cycling'.

Animals↗