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Biomedical subjects

A Hale

Publications and source records attributed to A Hale.

At least 19 recordsLinked to original sources
PubMed2006

Probing optical microfiber nonuniformities at nanoscale.

We demonstrate a novel, simple, and comprehensive method for probing optical microfiber surface and bulk distortions with subnanometer accuracy. The method employs a regular optical fiber as a probe that slides along a microfiber transmitting the fundamental mode. The fraction of radiation power absorbed in the probe depends on the local distribution of the mode propagating in the microfiber. From the measured variation of the absorbed power, we determine the variation of the effective microfiber radius, which takes into account both the microfiber radius and refractive index variations. Furthermore, we verify the cylindrical symmetry of the microfiber nonuniformities by probing the microfiber from different sides. These results explain observed transmission losses in silica microfibers and open broad opportunities for microfiber investigation.

Journal Article↗
PubMed2006

Sentinel laboratory surveillance of hepatitis C antibody testing in England: understanding the epidemiology of HCV infection.

This paper describes sentinel laboratory surveillance of hepatitis C antibody testing in England. Demographic and test result data were supplemented by follow-up questionnaires sent to the requesting clinician. Between October 2002 and September 2003 almost 75000 anti-HCV tests were performed in eight sentinel centres. More males were tested than females and over half of those tested were aged 25-44 years. Overall 5.7% (3333/58144, range 2.8-7.7%) individuals tested positive. Follow-up questionnaire data showed that 82% (1043/1277) of the positives had injecting drug use reported as the main risk exposure. The majority of negative individuals were undergoing routine screening as recommended for specific patient groups. Most individuals were asymptomatic. Antibody prevalence was estimated to be 34% in current injecting drug users and 42% in former injectors. Comparing positives to routine national surveillance suggests that only 53% (1782/3333) of diagnosed cases were reported. Sentinel laboratory data can provide valuable supplementary data to national surveillance.

Acute Disease↗
PubMed2006

Chick embryo lethal orphan virus can be polymer-coated and retargeted to infect mammalian cells.

Non-human adenovirus vectors have attractive immunological properties for gene therapy but are frequently restricted by inefficient transduction of human target cells. Using chicken embryo lethal orphan (CELO) virus, we employed a nongenetic mechanism of polymer coating and retargeting with basic fibroblast growth factor (bFGF-pc-CELOluc), a strategy that permits efficient tropism modification of human adenovirus. bFGF-pc-CELOluc showed efficient uptake and transgene expression in chick embryo fibroblasts (CEF), and increased levels of binding and internalization in a variety of human cell lines. Transgene expression was also greater than unmodified CELOluc in PC-3 human prostate cells, although the specific activity (RLU per internalized viral genome) was decreased. In CEF, the specific activity of bFGF-pc-CELOluc was considerably higher than in the human prostate cell line PC-3. Retargeted virus was fully resistant to inhibition by human serum with known adenovirus-neutralizing activity in vitro, while in mice CELOluc was cleared less rapidly from the blood than Adluc following i.v. administration in the presence of adenovirus neutralizing serum. Polymer coating and retargeting with bFGF further reduced rates of clearance for both viruses, suggesting protection against both neutralizing and opsonizing factors. The data indicate that CELO virus may be retargeted to infect human cells via alternative, potentially disease-specific, receptors and resist the effects of pre-existing humoral immunity.

ATPases Associated with Diverse Cellular Activitie↗
PubMed2002

Determination of the dose of agomelatine, a melatoninergic agonist and selective 5-HT(2C) antagonist, in the treatment of major depressive disorder: a placebo-controlled dose range study.

Agomelatine (S 20098) has a unique and new pharmacological profile. It is a melatoninergic agonist and selective antagonist of 5-HT2C receptors, and has been shown to be active in several animal models of depression. The aim of this study was to determine the active dose of agomelatine in the treatment of major depressive disorder (DSM-IV criteria). The methodology used was a conventional double-blind design comparing three different doses of agomelatine (1, 5 and 25 mg once a day) with placebo over an 8-week treatment period. Paroxetine was used as the study validator. Seven hundred and eleven patients with a baseline mean score of 27.4 on the 17-item Hamilton Rating Scale for Depression (HAM-D) were included. On the pivotal analysis, the mean final HAM-D total score (Full Analysis Set LOCF) demonstrated agomelatine 25 mg to be statistically more effective than placebo. This was confirmed by other analyses and criteria (responders, remission, subpopulation of severely depressed patients, Montgomery-Asberg Depression Rating Scale, Clinical Global Impression-Severity of Illness). Agomelatine 25 mg alleviated the anxiety associated with depression, as measured on Hamilton Anxiety Scale. Paroxetine was found to be effective on pivotal analysis and most of the secondary criteria used to validate the study methodology and population. Agomelatine, whatever the dose, showed good acceptability with a side-effects profile close to that of placebo. In conclusion, this study demonstrates that agomelatine is efficient in the treatment of major depressive disorder and that 25 mg is the target dose.

Acetamides↗
PubMed2002

Generation of recombinant virus-like particles of human and non-human polyomaviruses in yeast Saccharomyces cerevisiae.

OBJECTIVES: Non-viral methods of gene transfer have been preferred in gene therapy approaches for several reasons, particularly for their safety, simplicity and convenience in introducing heterologous DNA into cells. Polyomavirus virus-like particles (VLPs) represent a promising carrier for encapsidation of foreign nucleic acids for gene therapy. For the development of such gene delivery systems as well as for providing reagents for improving virus diagnostics, an efficient yeast expression system for the generation of different polyomavirus VLPs was established. METHODS: A galactose-inducible Saccharomyces cerevisiae yeast expression system was used. Formation of empty VLPs was confirmed by cesium chloride ultracentrifugation, agarose gel electrophoresis and electron microscopy. Cross-reactivity of the major capsid proteins (VP1) of different polyomaviruses was analyzed by Western blot using rabbit and mice sera raised against the VP1 proteins. RESULTS: VP1 of polyomaviruses from humans (JC polyomavirus and serotypes AS and SB of BK polyomavirus), rhesus monkeys (simian virus 40), hamsters (hamster polyomavirus), mice (murine polyomavirus) and birds (budgerigar fledgling disease virus) were expressed at high levels in yeast. Empty VLPs formed by all yeast-expressed VP1 proteins were dissociated into pentamers and reassociated into VLPs by defined ion and pH conditions. Different patterns of cross-reactivity of the VP1 proteins with heterologous mice and rabbit sera were observed. CONCLUSION: The developed heterologous yeast expression system is suitable for high-level production of polyomavirus VLPs. Yeast-derived VLPs are generally free of toxins, host cell DNA and proteins. These VLPs might be useful for the generation of new diagnostical tools, gene delivery systems and antiviral vaccines.

Amino Acid Sequence↗
PubMed2000

Distinct epidemiological patterns of Norwalk-like virus infection.

Norwalk-like viruses (NLV) are important economically as a cause of both sporadic gastroenteritis in the community and large outbreaks in hospitals and other institutional settings. Despite the description of several antigenic types relatively little is known about the epidemiology of these individual types. NLVs were detected by electron microscopy in faecal specimens from 706 outbreaks of gastroenteritis that represented 68% of all outbreaks of non-bacterial gastroenteritis. These outbreaks took place in the counties of West and North Yorkshire and Humberside during six winter seasons between July 1992 and June 1998. NLV strains from 671 outbreaks were typed by antigen capture enzyme linked immunosorbent assays (ELISA) based on antisera made to recombinant virus-like particles of three antigenically distinct NLVs; Norwalk (NV), Mexico (MXV) and Grimsby (GRV) viruses. GRV was the predominant strain for five of the six winter seasons and overall was associated with 61% of NLV outbreaks. MXV was responsible for a single epidemic peak in the winter of 1993/94 but was also observed at other times throughout the study period. NV was only associated with two outbreaks in 1994 that were epidemiologically linked. Strains from the remaining 32% of outbreaks were non-reactive in all three ELISA. Thus, a single NLV antigenic type seems to have predominated during the period 1992 to 1998 in the UK.

Adult↗
PubMed2000

The genomic sequence of a contemporary wild-type mumps virus strain.

Vaccination has the potential to eradicate mumps, and 82 countries now include a live attenuated mumps vaccine as part of their childhood vaccination programme. Although, monotypic, genetic variants of mumps virus (MuV) have been described based on comparison of the SH gene sequences, and at least seven genotypes have been identified. We now report the entire sequence of a recently isolated wild type MuV strain, Glouc1/UK96 (Glouc1) by direct sequencing of the cDNA obtained from cell culture fluid. The genome of this recent isolate was 15384 nucleotides in length. There were 579 nucleotide differences (3.8%) and 71 amino acid differences (1.5%) between Glouc1, a genotype G strain and Ur-AM9, a genotype B strain. Other MuV strains with available sequences were also compared with this pathological strain. The sequence of the contemporary strain reported here provides a picture of the variability of MuV over its entire genome (GenBank accession no. AF280799).

Genes, Viral↗
PubMed2000

Capsid protein diversity among Norwalk-like viruses.

We have determined the complete capsid gene sequence of 20 Norwalk-like viruses (NLVs) collected predominantly from outbreaks in the UK between 1989 and 1996. These comprised nine genogroup I and eleven genogroup II strains. Phylogenetic analysis of these and 15 published sequences suggest seven genomic sub-groups within genogroup I, including three previously described. In genogroup II, eight sub-groups were apparent, of which four were novel. Amino acid identities between strains of distinct genogroups ranged from 37 to 44% while varying between 61 and 100% for strains within a genogroup. Separate phylogenetic analyses of the N-terminus and central variable region of the capsid showed good correlation. Sequence divergence between strains was greatest within the central variable region, with amino acid sequence identities as low as 28% within a genogroup. These 15 genomic sub-groups provide a framework for further investigations of genetic and antigenic relationships within this calicivirus clade.

Amino Acid Sequence↗
PubMed1998

A histopathological assessment of the response of rectal adenocarcinoma to combination chemo-radiotherapy: relationship to apoptotic activity, p53 and bcl-2 expression.

AIMS: To investigate the use of pre-operative chemo-irradiation in downstaging advanced rectal cancer prior to surgical resection. METHODS: We examined the pathological effects of chemo-irradiation on 24 rectal tumours and correlated the efficacy of treatment with the level of apoptosis, mitosis, P53 and bcl-2 protein expression on pre-treatment biopsies. RESULTS: All tumours were resectable following chemo-irradiation. Six cancers showed complete regression with no viable tumour in the resection specimen. A significant correlation was found between spontaneous tumour apoptosis and tumour regression. CONCLUSIONS: Our results suggest that in rectal cancer the apoptotic rate in untreated tumour tissue may predict sensitivity to radiation and cytotoxic agents. No relationship was found between regression and mitotic rate, p53 or bcl-2 expression.

Adenocarcinoma↗
PubMed1997

Epidemiology of Mexico virus, a small round-structured virus in Yorkshire, United Kingdom, between January 1992 and March 1995.

The epidemiology of the small round-structured virus, Mexico virus (MxV), was investigated in North and West Yorkshire, United Kingdom, between January 1992 and March 1995 using a type-specific antigen ELISA. The results indicate that an epidemic of MxV occurred during the winter of 1993-1994, when this strain was associated with 45 of 99 outbreaks and sporadic childhood cases of gastroenteritis. Only 4 MxV-like isolates were found during the 1992-1993 winter season and none in the 1994-1995 season. This descriptive epidemiologic study suggests that MxV has an epidemic pattern of infection.

Caliciviridae↗
PubMed1997

In vitro drug adsorption to charcoal, silicas, acrylate copolymer and silicone oil with charcoal and with acrylate copolymer.

1. The relative binding constants of four drugs to charcoal, silicone oil silicas and acrylate copolymers was studied using an in-vitro binding technique. 2. The maximum adsorption capacity (K2) was chosen as a measure of the degree of binding and calculated by fitting to the Langmuir equation. 3. Charcoal alone was shown to be the most effective of the adsorbents chosen. The possible use of silicone oils as an adsorbent delivery vehicle in treatment of overdose is discussed.

Acetaminophen↗
PubMed1997

Prevalence of antibodies to HTLV in antenatal clinic attenders in south east London.

The prevalence of antibodies to HTLV in women attending a south east London antenatal clinic between October 1990 and July 1992 was determined using sera referred for routine rubella antibody testing. Samples were screened for HTLV antibody using a modified Fujirebio gel particle agglutination test and reactive sera confirmed by ELISA (Abbott Laboratories, North Chicago, IL) and two commercial Western blots (Cambridge Biotech Inc., Rockville, MD, and Diagnostic Biotechnology, Genelab Diagnostics, Louvaine, Belgium). This strategy confirmed the presence of HTLV-1 antibodies in 12 out of 6,289 sera (0.19%, 95% confidence limits 0.083% to 0.30%) and HTLV-2 antibodies in 2 (0.03%) sera. Specimens from 8 of 821 (0.97%, 95% confidence limits 0.42% to 1.9%) Afro-Caribbean women, three of 1,136 (0.26%, 95% confidence limits 0.055% to 0.78%) African women, and one of 3,049 (0.033%, 95% confidence limits 0.006% to 0.18%) Caucasian women were positive for HTLV-1 antibodies. Sera from Afro-Caribbean women born in the Caribbean were 7.6 times more likely to be HTLV-1 antibody positive than sera from Afro-Caribbean women born in the UK (P = 0.012). Selective testing of Afro-Caribbean and African antenatal clinic attenders, in this setting, would have identified 11 of the 12 HTLV-1 infections at an estimated cost of prevention of HTLV-1 associated disease of 100,000 pounds per case which is considerably less than the 1.3 million pounds which has been estimated to prevent a case by universal screening of UK blood donors.

Ambulatory Care Facilities↗
PubMed1995

Effect of red wine ingestion on the antioxidant capacity of serum.

Aerobic metabolism in biological systems produces reactive oxygen species, and defense against such prooxidants requires antioxidant activity, e.g., predominantly vitamins C and E in serum. Recently, flavonoids (polyphenols occurring widely in plants) have been investigated in vitro for their antioxidant activity; whether they are absorbed after ingestion is not clear. Using a chemiluminescent assay of serum antioxidant capacity (SAOC), we have studied the effects in normal individuals of ingesting red wine, white wine, and high doses of vitamin C. In nine subjects who ingested 300 mL of red wine, the mean SAOC was increased by 18% after 1 h and by 11% at 2 h. The same amount of white wine produced 4% and 7% increases, respectively. The ingestion of 1000 mg (5.7 mmol) of ascorbic acid by four subjects increased their mean SAOC by 22% at 1 h and by 29% at 2 h. An in vitro comparison of red wine, white wine, and various fruit juices showed the high antioxidant capacity of red wine in addition to its ability to increase the antioxidant capacity of serum in vivo. The antioxidant effects of various flavonoids and other polyphenols were also studied.

Adult↗