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Biomedical subjects

J Taylor

Publications and source records attributed to J Taylor.

At least 397 records · Page 22Linked to original sources

Terodiline causes polymorphic ventricular tachycardia due to reduced heart rate and prolongation of QT interval.

Recent reports have suggested an association between terodiline hydrochloride and cardiac arrhythmias. We report 4 patients presenting over a six month period who developed polymorphic ventricular tachycardia (polymorphic VT) while receiving treatment with this agent. In each case there was prolongation of QT interval on electrocardiogram (ECG). Two patients had hypokalaemia associated with diuretic therapy. In the 3 cases in which follow-up ECG was available, QT interval returned to normal after discontinuation of terodiline. In order to define the effects of terodiline on corrected QT interval (QTc) and heart rate in the elderly, a prospective study was performed in 8 elderly in-patients treated with terodiline for urinary incontinence. After 7 days treatment with terodiline 12.5 mg twice daily, there was a significant increase in QT by a mean of 29 ms, QTc by 15 ms and a decrease in resting heart rate by a mean of 6.7 beats.min-1. Terodiline increases QTc and reduces resting heart rate in elderly patients. Both these effects may be associated with polymorphic VT, a potentially life threatening arrhythmia. This drug should be avoided in patients with other known risk factors for polymorphic VT, particularly hypokalaemia and cardiac disease.

Aged↗

Dipyridamole increases human red blood cell deformability.

An automated filtration technique has been used to investigate the effect of dipyridamole (DP) on red blood cell deformability in patients identified as having rigid red cells. They were patients on haemodialysis (HD) for chronic renal failure (n = 18), patients with peripheral vascular disease (PVD, n = 23) and controls (hospital outpatients, n = 33). Leucocytes and platelets were removed from heparinised blood by filtration through Imugard wool. Washed red cell suspensions in buffer at 5% haematocrit, without or with 5 microM DP, were filtered through Nuclepore Hemafil Membranes with 4.7 microns pores. The initial steady state relative filtration pressure (iRFP) was used to assess cell deformability. A low iRFP value reflects increased deformability and vice versa. The mean iRFP values were 0.33, 0.393 and 0.403 for controls, PVD and HD patients respectively, indicating that the red cells in the two groups of patients were significantly more rigid. DP reduced the iRFP to 0.266, 0.278 and 0.263 for controls, PVD and HD patients respectively. The results suggest that DP may be beneficial when red cell rigidity contributes to impaired microvascular perfusion.

Adult↗

Aboriginal migration and labour market programs.

"Despite the potential for government employment policies both to encourage and preclude migration among the Aboriginal workforce, little is known about the impacts of such policies. This paper seeks to construct a base line for identifying these impacts by establishing the spatial structure of labour migration among the Aboriginal and Torres Strait Islander population. It makes use of 1986 Census data to describe the volume and pattern of net and gross flows of working-age Aborigines and Islanders through the national settlement system, distinguishing between movements in remote and closely settled parts of the country. Full determination of the links between policy and migration flows awaits comparison with 1991 Census results."

Australia↗

Nonreplicating viral vectors as potential vaccines: recombinant canarypox virus expressing measles virus fusion (F) and hemagglutinin (HA) glycoproteins.

The development of canarypox virus (CPV) recombinants expressing the hemagglutinin (HA) and fusion (F) glycoproteins of measles virus (MV) is described. Inoculation of the CPV-MV recombinants into avian or nonavian tissue culture substrates led to the expression of authentic MVF and MVHA as determined by radioimmunoprecipitation and surface immunofluorescence. In contrast to avian-derived tissue culture, no productive replication of the CPV recombinant was evident in tissue culture cells derived from nonavian origin. On inoculation of dogs, a species restricted for avipoxvirus replication, the recombinants elicited a protective immune response against a lethal canine distemper virus (CDV) challenge. The level of MV neutralizing antibodies and the level of protection induced against CDV challenge achieved by the host-restricted CPV vector were equivalent to that obtained by vaccinia virus vectors expressing the same MV antigens.

Animals↗

NYVAC: a highly attenuated strain of vaccinia virus.

A highly attenuated vaccinia virus strain, NYVAC (vP866), was derived from a plaque-cloned isolate of the Copenhagen vaccine strain by the precise deletion of 18 open reading frames (ORFs) from the viral genome. Among the ORFs deleted from NYVAC (vP866) are two genes involved in nucleotide metabolism, the thymidine kinase (ORF J2R) and the large subunit of the ribonucleotide reductase (ORF I4L); the gene encoding the viral hemagglutinin (ORF A56R); the remnant (ORF A26L) of a highly expressed gene responsible for the formation of A-type inclusion bodies; the disrupted gene (ORFs B13R/B14R) normally encoding a serine protease inhibitor; and a block of 12 ORFs bounded by two known viral host range regulatory functions (ORFs C7L through K1L). Within this block a secretory protein (ORF N1L) implicated in viral virulence and a functional complement 4b binding protein (ORF C3L) are encoded. The ORFs were deleted in a manner which prevents the synthesis of undesirable novel gene products. The attenuation characteristics of the derived NYVAC strain were compared in in vitro and in vivo studies with those of the Western Reserve (WR) laboratory strain, the New York City Board of Health vaccine strain (Wyeth), the parental plaque-cloned isolate (VC-2) of the Copenhagen vaccine strain used to derive NYVAC, and the avipox virus canarypox (ALVAC), which is naturally restricted for replication to avian species. The NYVAC strain was demonstrated to be highly attenuated by the following criteria: (a) no detectable induration or ulceration at the site of inoculation on rabbit skin; (b) rapid clearance of infectious virus from the intradermal site of inoculation on rabbit skin; (c) absence of testicular inflammation in nude mice; (d) greatly reduced virulence as demonstrated by the results of intracranial challenge of both 3-week-old or newborn mice; (e) greatly reduced pathogenicity and failure to disseminate in immunodeficient (nude or cyclophosphamide treated) mice; and (f) dramatically reduced ability to replicate on a variety of human tissue culture cells. Despite these highly attenuated characteristics, the NYVAC strain, as a vector, retains the ability to induce strong immune responses to extrinsic antigens.

Animals↗

P300 and traffic scenes: the effect of temazepam.

The present research investigated the effects of a minor tranquillizer (temazepam) on P300 in a paradigm that may be relevant for traffic behaviour. Because accident scenes have not been used previously in P300 research, Experiment 1 (n = 8) examined whether the P300 elicited by safe traffic scenes and scenes of imminent road accidents were sensitive to the probability of occurrence. Event-related potentials were recorded from C3, Cz, C4, P3, Pz and P4 within an oddball paradigm. The type of stimulus to which subjects responded (pictures of imminent accidents or safe road scenes) was crossed with the probability (0.1 or 0.5) of the relevant (to which a response was required) event. The results indicated that P300 amplitude increased with decreasing probability of the relevant stimulus and that P300 was most pronounced at Pz. Experiment 2 (n = 12) employed a drug treatment (10 mg temazepam) and a placebo treatment (100 mg Vitamin E). An oddball paradigm with a probability of the relevant stimulus of 0.1 was used and P300 was recorded from Cz, C3, C4, Pz, P3 and P4. Generally, the ingestion of temazepam decreased P300 amplitude and increased P300 latency at all sites. Reaction time, on the other hand, was not influenced by drug administration. The data demonstrate the clear effect of minor tranquillizers on the psychological processes associated with P300.

Accidents, Traffic↗

The image of self and of the environment in drug abusers: a comparative study using the TAT.

This study attempted to add to our understanding of the heroin abusers' identity problems, using images of the self and the environment. Murray's Thematic Apperception Test (TAT) was applied to a group of male drug users undergoing withdrawal treatment with methadone and also to a group of male, non-drug using controls. The needs of the subjects and the demands of the environment, plus interaction between the two, were compared between the two groups to obtain information about the self and lifestyle. Among the data which emerged, is an increased need for destructive aggression and an environment experienced as coercive and emarginating. Among the interactions we observed coerced imagination, difficulties in identification, personal relationships based on abandonment with persecutory projection of the female figure and a tendency toward immature defences such as avoidance, denial and acting out. This information is discussed in relation to possible means of treatment.

Adult↗

Human leukocyte antigen-DRB1*1104 in the chronic iridocyclitis of pauciarticular juvenile rheumatoid arthritis.

To determine whether genetic markers for chronic iridocyclitis could be identified, we used both serologic and oligonucleotide dot blot techniques to characterize immunogenetically 164 children with early-onset pauciarticular juvenile rheumatoid arthritis. Seventy-eight children (47.6%) had chronic iridocyclitis and 86 (52.4%) had not had evidence of eye disease during a mean follow-up period after the onset of arthritis of 15.8 years (minimum of 5.5 years). Control subjects were 218 healthy, unrelated individuals. The analysis was limited to alleles known to be associated with an increased or decreased risk of early-onset pauciarticular juvenile rheumatoid arthritis or of chronic iridocyclitis in this form of juvenile rheumatoid arthritis. Only one split of human leukocyte antigen (HLA)-DR5, HLA-DRB1* 1104, showed a statistically significant association with a risk of chronic iridocyclitis (chi-square value = 7.52; p = 0.036 adjusted; odds ratio 3.45); HLA-DQA1* 0501 and HLA-DQB1* 0301, both in linkage disequilibrium with HLA-DRB1* 1104, also were significantly associated with eye disease. Patients with both the DRB1* 1104 and DPB1* 0201 genes had a 7.7-fold increased risk for chronic iridocyclitis compared with that for other patients. The presence of HLA-DRB1* 1104 was about four times as specific, but only about one third as sensitive, as antinuclear antibodies in identifying patients at risk for eye disease. Although all children with early-onset pauciarticular juvenile rheumatoid arthritis should undergo periodic slit-lamp examinations, those with the HLA class II gene DRB1* 1104 are at particularly high risk for eye disease, and we recommend that they be monitored carefully for its evolution.

Adult↗

Resistance of hepatitis delta virus replication to interferon-alpha treatment in transfected human cells.

Interferon-alpha (IFN-alpha) is known to inhibit both DNA and RNA viruses, including hepatitis B virus (HBV). In humans the antiviral effect, if any, of IFN-alpha on hepatitis delta virus (HDV) is complicated by the fact that HDV is spread only to patients already infected with HBV. An in vitro model system was used to assay for an antiviral effect of IFN-alpha on HDV genome replication. Hep G2 cells were transfected with a plasmid containing a trimer of HDV and treated with IFN (20 or 100 units/mL) starting 1-7 days after transfection. RNA extracted from treated and nontreated cells was assayed by both slot blot and Northern analyses. The IFN-alpha treatment as expected increased the 2'-5' oligo A synthetase RNA activity, but it did not affect HDV genome replication. Thus, in the absence of HBV, it appears that HDV is resistant to IFN-alpha.

2',5'-Oligoadenylate Synthetase↗

Evidence for reversibility of defective counterregulation in a patient with insulinoma.

To investigate her unheralded neuroglycopenia, a 45-year-old woman was studied before and 3 months after removal of her insulinoma. Hypoglycaemia was induced and reversed by glucose infusion during 4-h insulin infusions (1.5 mU kg-1 min-1). Postoperatively, the low preoperative adrenaline, noradrenaline, growth hormone, and cortisol responses increased by 490, 152, 64, and 178%, respectively, and started at higher glucose levels (2.7 vs 1.9 mmol l-1 for adrenaline), with a four-fold increase in autonomic symptoms and more profound psychomotor dysfunction. We conclude that the syndrome of recurrent severe hypoglycaemia with defective warning symptoms and hormonal responses, in this case induced by an insulin-secreting tumour, is reversible, perhaps by the removal of the hypoglycaemia, a finding which may be relevant to other patients with recurrent severe hypoglycaemia.

Blood Glucose↗

Knowledge, expectations and experiences of patients receiving chemotherapy for breast cancer.

The experiences of a cohort of 60 women receiving chemotherapy in treatment of breast cancer were monitored in an in-depth prospective study. The purpose of the investigation was to identify ways in which nurses could improve the preparation and support of patients undergoing chemotherapy. It was found that patients' knowledge of chemotherapy was limited and that the side-effects they experienced, and their reactions to these, were rather different and more diverse than had been expected. The study illustrates the value of exploring patients' perceptions of their problems and needs for information and support.

Adult↗

Assembly of hepatitis delta virus particles.

Hepatitis delta virus (HDV) is a subviral satellite of hepatitis B virus (HBV). Since the RNA genome of HDV can replicate in cultured cells in the absence of HBV, it has been suggested that the only helper function of HBV is to supply HBV coat proteins in the assembly process of HDV particles. To examine the factors involved in such virion assembly, we transiently cotransfected cells with various hepadnavirus constructs and cDNAs of HDV and analyzed the particles released into the medium. We report that the HDV genomic RNA and the delta antigen can be packaged by coat proteins of either HBV or the related hepadnavirus woodchuck hepatitis virus (WHV). Among the three co-carboxy-terminal coat proteins of WHV, the smallest form was sufficient to package the HDV genome; even in the absence of HDV RNA, the delta antigen could be packaged by this WHV coat protein. Also, of the two co-amino-terminal forms of the delta antigen, only the larger form was essential for packaging.

Antigens, Viral↗

Reverse transcriptase of human immunodeficiency virus type 1: functionality of subunits of the heterodimer in DNA synthesis.

From an in vitro analysis of the DNA-synthesizing abilities of certain specifically mutated forms of the heterodimeric reverse transcriptase of human immunodeficiency virus type 1, we can conclude that in a heterodimer, the functionality of p66 is necessary while the functionality of the p51 subunit is not needed. Conversely, p51 is not able to catalyze DNA synthesis when associated with p66, and yet when the p66 protein is absent, p51 can function. These conclusions applied to DNA synthesis on heteropolymeric RNA and DNA templates.

Acquired Immunodeficiency Syndrome↗

When retroviral reverse transcriptases reach the end of their RNA templates.

Luo and Taylor (J. Virol. 64:4321-4328, 1990) have previously shown that when, during RNA-directed DNA synthesis, a retroviral reverse transcriptase comes to a halt at the end of an RNA template, the associated RNase H produces a specific oligonucleotide that contains the 5' end of that template; in those studies the length of the oligonucleotide was predominantly 17 nucleotides. We have now investigated variables that might affect the formation and length of such a terminal oligonucleotide. We found small but significant variations in the length could be caused by the choice of reaction conditions and also the sources of reverse transcriptase and RNA template. Nevertheless, the general finding in all these situations was that RNase H acted at or about 14 to 18 nucleotides from the 5' end, thereby supporting the interpretation that in the reverse transcriptase, the cleavage site for the RNase H is held at around this distance behind the DNA polymerase activity. In other words, it appears that for the intact protein, the RNase H and reverse transcriptase activities may work in a coupled or coordinate manner. We also found that more than 80% of the residual 5' oligonucleotides remained base paired to the RNA-directed DNA product. Furthermore, under certain conditions, these short RNAs could act as efficient primers for an associated DNA-directed DNA synthesis in the reverse direction.

Base Sequence↗

Editing on the genomic RNA of human hepatitis delta virus.

It has been shown previously that during replication of the genome of human hepatitis delta virus (HDV), a specific nucleotide change occurs to eliminate the termination codon for the small delta antigen (G. Luo, M. Chao, S.-Y. Hsieh, C. Sureau, K. Nishikura, and J. Taylor, J. Virol. 64:1021-1027, 1990). This change creates an extension in the length of the open reading frame for the delta antigen from 195 to 214 amino acids. These two proteins, the small and large delta antigens, have important and distinct roles in the life cycle of HDV. To further investigate the mechanism of this specific nucleotide alteration, we developed a sensitive assay involving the polymerase chain reaction to monitor changes on HDV RNA sequences as they occurred in transfected cells. We found that the substrate for the sequence change was the viral genomic RNA rather than the antigenomic RNA. This sequence change occurred independently of genome replication or the presence of the delta antigen. Less than full-length genomic RNA could act as a substrate, but only if it also contained a corresponding RNA sequences from the other side of the rodlike structure, which is characteristic of HDV. We were also able to reproduce the HDV base change in vitro, by addition of purified viral RNA to nuclear extracts of cells from a variety of species.

Animals↗