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Biomedical subjects

J Arthur

Publications and source records attributed to J Arthur.

At least 19 recordsLinked to original sources
PubMed1997

Transduction of murine and human tumors using recombinant adenovirus vectors.

BACKGROUND: Most cytokine-based cancer gene therapy clinical trials have used labor-intensive, retrovirus-mediated strategies resulting in unpredictable gene expression. Recombinant AdV vectors were evaluated for easier, more reproducible gene transfer into 12 human melanoma, 2 murine fibrosarcomas, and 8 other tumor cell lines. METHODS: AdV vectors contained a reporter (Escherichia coli beta-galactosidase or firefly luciferase) or cytokine gene (human interleukin-2 [IL-2] or IL-7). Transduction efficiencies and expression levels were assessed by histochemical staining, flow cytometry, polymerase chain reaction, fluorometry, and enzyme-linked immunosorbent assay. Tumorigenicity was determined by subcutaneous injection of cells into syngeneic mice. RESULTS: All cell lines studied were transduced with AdV. Most cell lines exhibited 100% transduction efficiencies (by flow cytometry) at multiplicities of infection (MOI) epsilon 10. Gene expression correlated linearly with MOI, but a cytopathic effect was observed at MOI > 100 with all vectors. Nanogram gene expression levels were routinely achieved. Irradiation (30 Gy) minimally affected expression levels. Tumorigenicity of AdV-IL-2-transduced fibrosarcoma cells in mice was inversely related to IL-2 production. A majority of mice that rejected their tumor challenge were immune to tumor rechallenge. CONCLUSIONS: E1-deleted AdV vectors may prove useful in generating tumor vaccines ex vivo with high, transient cytokine expression levels.

Adenoviridae↗
PubMed1995

Efficacy, safety, and immunogenicity of a meningococcal group B (15:P1.3) outer membrane protein vaccine in Iquique, Chile. Chilean National Committee for Meningococcal Disease.

A meningococcal group B (15:P1.3) outer membrane protein vaccine was tested for efficacy in a randomized, double-blind controlled study in Iquique, Chile. A total of 40 811 volunteers, ages 1-21 years, enrolled in the study. Volunteers received two doses of vaccine six weeks apart by jet injector. Both the experimental vaccine and the control vaccine (Menomune, A, C, Y and W135 meningococcal polysaccharide vaccine) were well tolerated with minor side-effects. Active surveillance for suspected cases of meningococcal disease was conducted for 20 months in Iquique. Eighteen cases of group B meningococcal disease were confirmed during the 20 months. Efficacy was estimated to be 51% (p = 0.11) for all ages combined. In children aged 1-4 no protection was evident, but in volunteers aged 5-21 vaccine efficacy was 70% (p = 0.045). The IgG antibody response by ELISA was characterized by a large booster effect after the second dose, followed by a substantial drop in antibody levels by 6 months. The youngest children had the highest responses. The bactericidal antibody response, on the other hand, was characterized by the lack of a significant booster response, higher responses in the older children, and an increase in the geometric mean titer in the later months of the study in the older children.

Adolescent↗
PubMed1995

Characterization of a gene encoding a cysteine-rich keratin associated protein synthesized late in rabbit hair follicle differentiation.

Many different cysteine-rich proteins are synthesized during hair follicle differentiation, forming part of the interstitial matrix between bundles of intermediate filaments. We have isolated a rabbit gene (rKAP4L), a member of a multigene family that encodes a small cysteine-rich hair keratin associated protein. This is the first complete gene sequence for this family. The rKAP4L gene is expressed in the cortex of rabbit pelage hair follicles at a late stage of hair follicle differentiation, well after the synthesis of the other major hair proteins, the intermediate filament and glycine/tyrosine-rich keratin associated proteins, has commenced. The protein contains 36 mol % cysteine, with a molecular size of 13593 daltons, and its sequence appears to be based on a pentapeptide repeat. It is predicted to adopt a folded conformation characterized by beta-turns interspersed with short stretches of beta-sheet or random coil.

Amino Acid Sequence↗
PubMed1994

Clinical utility of digital dobutamine stress echocardiography in the noninvasive evaluation of coronary artery disease.

Exercise electrocardiography is an established mode of evaluation for patients with suspected coronary artery disease. It also provides prognostic information and guides therapeutic management in patients with established disease. However, some patients are unable to exercise because of orthopedic problems, neurologic diseases, peripheral vascular disease, or deconditioning. In the past, these patients have been referred for angiography to help assess their disease. Recently, however, new techniques to assess myocardial perfusion and/or function, including stress echocardiography, have been used in the noninvasive assessment of coronary artery disease in this group of patients. Echocardiography has been used in combination with different drugs, including dobutamine, dipyridamole, and adenosine. Dobutamine is probably the single most studied drug for stress echocardiography. Dobutamine stress echocardiography is a safe, feasible, and valuable technique for evaluating coronary artery disease.

Clinical Trials as Topic↗
PubMed1994

The prevalence of ST-segment depression on ambulatory electrocardiographic monitoring during daily life in high-risk asymptomatic police officers.

BACKGROUND: In individuals with no known ischaemic heart disease, the prevalence and significance of ST-segment depression on ambulatory electrocardiographic monitoring is unclear. We therefore determined the prevalence of ST-segment depression among middle-aged male police officers, an occupational group in whom an increased risk of ischaemic heart disease has been reported, who also had multiple individual coronary risk factors but no known ischaemic heart disease. METHODS: Full-time male police offices aged 45 years or more with at least two coronary risk factors but no known ischaemic heart disease performed a 24h ambulatory electrocardiographic monitor, timed to include a shift of work. The number and duration of episodes of ST-segment depression were determined. In those in whom ST-segment depression was detected, exercise thallium scintigraphy and repeat 24h ambulatory electrocardiographic monitoring were performed. RESULTS: The prevalence of ST-segment depression on 24h ambulatory electrocardiographic monitoring, including an 8h period of normal work, was 3.4% (95% confidence interval 1.3-8.3%). Exercise thallium scintigraphy was carried out in those in whom ST-segment depression had been detected. Despite two participants developing ST-segment depression during exercise, no evidence of myocardial ischaemia was observed on the perfusion scan. Therefore, the prevalence of ST-segment depression on ambulatory electrocardiographic monitoring in this asymptomatic but high-risk population was low and, when it did occur, no exercise-induced myocardial ischaemia was observed. CONCLUSION: These results suggest that ST-segment depression on ambulatory electrocardiographic monitoring in asymptomatic subjects may not represent myocardial ischaemia. The use of this parameter to screen asymptomatic populations for ischaemic heart disease is therefore highly questionable.

Activities of Daily Living↗
PubMed1993

Comparison of propofol with thiopentone for treatment of bupivacaine-induced seizures in rats.

Thirty Sprague-Dawley rats were paralysed with pancuronium and their lungs ventilated mechanically with 70% nitrous oxide and 0.5% halothane in oxygen. Bupivacaine 2 mg kg-1 min-1 was infused continuously i.v. until the animals died. At the onset of seizures, animals were given an i.v. bolus of propofol 1 mg kg-1 (n = 10), thiopentone 2 mg kg-1 (n = 10) or lipid vehicle (n = 10). Administration of propofol or thiopentone was repeated each time seizures restarted and lipid vehicle administrations were repeated at 2-min intervals until the electroencephalogram became isoelectric. All animals developed seizures, arrhythmias, isoelectric EEG and asystole. Administration of lipid vehicle induced no obvious changes in ongoing epileptiform activity. The initial doses of thiopentone and of propofol stopped epileptiform activity in all animals, usually within 6 s after administration. The seizure-free period after the initial administration of thiopentone and of propofol lasted, on average, 0.98 min and 1.72 min, respectively. We conclude that propofol may have value in treating seizures induced by bupivacaine.

Animals↗
PubMed1993

Intranuclear foci containing low abundance herpes simplex virus latency-associated transcripts visualized by non-isotopic in situ hybridization.

During latent infection of neurons with herpes simplex virus type 1 (HSV-1), several RNA transcripts of varying abundance arise from a single locus within the virus repeats. The functions of latency-associated transcripts (LATs) are unknown and the relationship between the various RNA species requires further clarification. Reported here is a novel approach to the study of HSV transcripts during latency, based on the increasing realization that cellular and viral RNAs are synthesized and processed by macromolecular complexes that occupy discrete compartments within the nucleoplasm of a cell. High resolution non-isotopic in situ hybridization was used to study the intranuclear topology of HSV-1 LATs in primary sensory neurons of latently infected mice and humans. Low abundance (minor) LATs were localized to sharply defined intranuclear foci of 1 to 3 microns in diameter. On average, there were 2.6 to 2.8 foci/LAT+ neuronal profile (5 microns), representing 13 to 14 foci/cell. In contrast to the focal deployment of minor LATs, the more abundant latency-associated RNAs were distributed diffusely throughout the nucleoplasms of latency infected neurons, with prominent sparing of nucleolar regions. These data establish a foundation for studying the synthesis, processing and transport of LATs in vivo. It should now be possible to investigate the nature of those cellular products which associate with HSV-1 encoded LATs in vivo and thereby determine whether minor LATs are associated with previously characterized macromolecular complexes, such as those responsible for processing of pre-messenger RNA.

Animals↗
PubMed1993

A randomised prospective study comparing the new vacuum extractor policy with forceps delivery.

OBJECTIVE: To compare assisted vaginal delivery by forceps with delivery by vacuum extractor, where a new vacuum extractor policy was employed which dictated the cup to be used in specific situations. DESIGN: Multicentre randomised controlled trial. SETTING: Four district general hospitals in the West Midlands. SUBJECTS: Six hundred-seven women requiring assisted vaginal delivery, of whom 296 were allocated to vacuum extractor delivery and 311 to forceps. MAIN OUTCOME MEASURES: Delivery success rate, maternal perineal and vaginal injuries, maternal anaesthetic requirements, neonatal scalp and facial injuries. RESULTS: Of the vacuum extractor group, 85% were delivered by the allocated instrument compared to 90% in the forceps group (odds ratio (OR) 0.64; 95% confidence intervals (CI) 0.4-1.04). However, more women in the vacuum extractor group were delivered vaginally (98%) than in the forceps group (96%). There were significantly fewer women with anal sphincter damage or upper vaginal extensions in the vacuum extractor group (11% vs 17%, OR 0.6; 95% CI, 0.38-0.97). There were significantly fewer women in the vacuum extractor group requiring epidural or spinal anaesthetics (25.4% vs 32.7%, OR 0.69; 95% CI 0.49-0.99) or general anaesthetics (1% vs 4%, OR 0.17; 95% CI 0.04-0.76). Although there were significantly more babies in the vacuum extractor group with cephalhaematomata (9% vs 3%, OR 3.3; 95% CI 1.4-7.4) there were fewer babies in the vacuum extractor group with other facial injuries. There were three babies in the forceps group with unexplained neonatal convulsions. CONCLUSIONS: Assisted vaginal delivery using the new vacuum extractor policy is associated with significantly less maternal trauma than with forceps. Further studies are required to assess neonatal morbidity adequately.

Adult↗
PubMed1992

Foodhandling practices of Dunedin caterers: a cause for concern.

AIM: Foodhandling practices in the Dunedin catering industry were assessed to determine if they were correct, preventing the transmission of foodborne disease to the public. METHOD: A random sample of 300 foodservice outlets was selected. Information was collected during personal interviews with managers using a prepared questionnaire. Potentially dangerous practices were further analysed and summed to identify "at risk" operations. RESULTS: Response rate was 71%. Thirty-six percent of restaurants, 27% of takeaway bars and 25% of deli-bars and butchers could have been considered at risk operations. Few managers had any formal training in preparing and serving food, and less than 20% of managers and personnel had any food hygiene training. CONCLUSIONS: Current legislation and its enforcement is unable to adequately address incorrect food handling practices. It is recommended that revisions of the law emphasise the importance of correct practices and their enforcement. Food hygiene training should become compulsory for all who work in the catering industry.

Cooking↗
PubMed1992

Two patterns of persistence of herpes simplex virus DNA sequences in the nervous systems of latently infected mice.

The number of herpes simplex virus (HSV) genome equivalents recovered from latently infected mouse spinal ganglia was compared with the proportion of neurons containing latency-associated transcripts (LATs). Two distinct patterns of HSV persistence were observed, depending on the anatomical location of ganglia with respect to the site of cutaneous inoculation. The location of the bulk of latent viral DNA did not correspond with the highest prevalence of LAT+ neurons. Viral DNA was most abundant in spinal ganglia directly innervating the inoculation site and the amount recovered, which was similar to that found previously in human trigeminal ganglia, suggested that LAT+ neurons each contain hundreds of copies of HSV DNA. In stark contrast, although LAT+ neurons were most abundant in neighbouring ganglia, viral DNA was scarce (approx. 20 copies/LAT+ cell). These data indicate that amplification of HSV DNA sequences is greatest in ganglia previously shown to be associated with viral antigen expression during the productive phase of primary infection.

Animals↗
PubMed1990

Amebiasis at an evacuation site on the Thai-Cambodian border.

Symptomatic intestinal amebiasis was highly endemic among the Cambodians living at Green Hill, an evacuation site on the Thai-Cambodian border between June 1987 through May 1989. Monthly incidence rates of intestinal amebiasis were determined to be inversely proportional to cumulative monthly rainfall. The highest incidence of amebic dysentery was 63/1000 in children 12-23 months old. Behavioral risk factors were investigated by conducting a case-control study. A questionnaire was administered to 73 families, each having at least one member with confirmed intestinal amebiasis within the past 3 months, and to 95 randomly selected control families having no individual with diarrhea for at least 3 months. Individuals from families with greater than 4 members were at higher risk for acquiring intestinal amebiasis. No significant differences in behavioral risk factors were identified between case and control families. Eighty-six percent of 51 water samples drawn from wells where amebiasis patients obtained their drinking water had greater than 10 coliforms/100 ml. The main route of transmission of E. histolytica was not identified, but was most likely via the fecal-oral route.

Adolescent↗