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Biomedical subjects

R Jackson

Publications and source records attributed to R Jackson.

At least 199 records · Page 11Linked to original sources
PubMed1996

A study of the topography of the lymphatic system of the Australian brushtail possum (Trichosurus vulpecula).

The superficial and deep lymphatic systems of the Australian brushtail possum (Trichosurus vulpecula) are described. In common with other marsupials studied to date and in contrast with most eutherians, there were no popliteal lymph nodes and efferent drainage from the inguinal lymph centre passed directly to the deep axillary group of lymph nodes via an inguinoaxillary trunk. Efferent vessels from the tonsil passed directly to the deep cervical lymph node, which was drained by the tracheal trunk. The mandibular and parotid lymph nodes drained independently to the superficial cervical lymph node. All subcutaneous lymph drainage passed either through the superficial cervical or the axillary lymph centres before entering the venous system, an arrangement which is also found in kangaroos. The significance of the patterns of lesion distributions in possums with naturally occurring tuberculosis caused by Mycobacterium bovis is discussed.

Abdomen↗
PubMed1995

Fletcher Challenge-University of Auckland Heart & Health Study: design and baseline findings.

AIMS: The aims of this prospective observational study are to determine the relationship of sociodemographic factors, psychological factors and several factors measured in blood, with the risk of coronary heart disease (CHD) in a New Zealand population. METHODS: Participants were recruited from two sources: employees of the Fletcher Challenge Group and individuals listed on the general electoral roll for the Auckland region. Baseline and follow up risk factor data were obtained from a questionnaire, blood samples and a simple physical examination. Outcome data on deaths and hospitalisations due to coronary heart disease will be obtained primarily through linkage of participant identifiers to data collected nationally by the New Zealand Health Information Service. RESULTS: A total of 10,529 individuals agreed to participate (8011 from Fletcher Challenge and 2518 from the electoral roll), representing a response rate of 74%. Within the study population, there was a broad distribution of sociodemographic characteristics including ethnicity-10% of participants were Maori and 5% were of Pacific Islands origin. There was also wide heterogeneity of coronary heart disease risk as judged from the distributions of established risk factors at baseline-5% of participants had evidence of existing coronary heart disease, a quarter were current smokers, a sixth were nondrinkers, almost a half were overweight, a fifth had blood pressure > or = 150/95 mmHg or were receiving antihypertensive treatment and a sixth had cholesterol levels > or = 6.5 mmol/L. CONCLUSIONS: This is the first, large scale prospective observational study of the determinants of coronary heart disease in a New Zealand population. The study participants represent a broad cross section of society, with wide variation in sociodemographic characteristics and coronary heart disease risk. Initial results concerning the relationships of primary interest should be available within 5 years when sufficient coronary heart disease events have been documented to allow reliable analyses.

Adult↗
PubMed1995

Interleukin 2 induces CD8+ T cell-mediated suppression of human immunodeficiency virus replication in CD4+ T cells and this effect overrides its ability to stimulate virus expression.

The nonlytic suppression of human immunodeficiency virus (HIV) production from infected CD4+ T cells by CD8+ lymphocytes from HIV-infected individuals is one of the most potent host-mediated antiviral activities observed in vitro. We demonstrate that the pleiotropic cytokine interleukin 2 (IL-2), but not IL-12, is a potent inducer of the CD8+ HIV suppressor phenomenon. IL-2 induces HIV expression in peripheral blood or lymph node mononuclear cells from HIV-infected individuals in the absence of CD8+ T cells. However, IL-2 induces CD8+ T cells to suppress HIV expression when added back to these cultures, and this effect dramatically supersedes the ability to IL-2 to induce HIV expression. Five to 25 times fewer CD8+ cells were required to obtain comparable levels of inhibition of viral production if they were activated in the presence of IL-2 as compared with IL-12 or no exogenous cytokine. Furthermore, IL-2 appeared either to induce a qualitative increase in HIV suppressor cell activity or to increase the relative frequency of suppressor cells in the activated (CD25+) CD8+ populations. Analyses of proviral levels in peripheral blood mononuclear cells suggest that CD8+ T cell-mediated lysis of in vivo infected cells is not induced by IL-2. These results have implications for our understanding of the effects of impaired IL-2 production during HIV disease as well as the overall effects of IL-2-based immunotherapy on HIV replication in vivo.

CD4-Positive T-Lymphocytes↗
PubMed1995

Trends in coronary heart disease risk factors in Auckland 1982-94.

AIMS: This paper describes trends in major coronary heart disease risk factors over the period 1982 to 1994 in the city of Auckland, New Zealand. METHODS: Coronary heart disease risk factor levels were measured in three cross-sectional surveys in Auckland in 1982, 1986-8 and 1993-4, following a standardised protocol. Random samples of nonMaori, nonPacific Island adults aged 35-64 years were selected from the Auckland general electoral rolls using similar methods in all three surveys. Participants attended a study centre for interview and risk factor measurement. RESULTS: The analyses presented are based on samples of 1029 men and 569 women in 1982, 541 men and 365 women in 1986-8, and 712 men and 685 women in 1993-4. The data are directly age-standardised to the 1986 New Zealand population. Over the 12 year period the prevalence of self-reported cigarette consumption declined significantly from 28.6% to 16.9% in men and from 24.5% to 14.8% in women. Mean serum total cholesterol showed little change between 1982 and 1986-8 but declined significantly between 1986-8 and 1993-4 by approximately 6% from 6.12 mmol/L to 5.73 mmol/L in men and by 9% from 6.17 mmol/L to 5.60 mmol/L in women. Mean serum high density lipoprotein (HDL) cholesterol showed a modest increase between 1982 and 1986-8 but declined significantly between 1986-8 and 1993-4 by 12% from 1.25 mmol/L to 1.10 mmol/L in men and by 9% from 1.55 mmol/L in women to 1.40 mmol/L in women. The total cholesterol to HDL cholesterol ratio increased significantly between 1986-8 and 1993-4 by 6% in men but showed little change in women. Mean blood pressure levels fell by 4-6 mmHg systolic and 6-7 mmHg diastolic over the 12 year period in men and women. Mean body mass index increased significantly from 25.6 to 26.4 in men and from 24.5 to 25.1 in women during this period. CONCLUSIONS: Over the 12 year period, 1982-94 there have been substantial reductions in the prevalence of self reported cigarette smoking, mean serum total cholesterol levels and mean blood pressure levels in middle aged Aucklanders. Of concern, the prevalence of obesity has increased and mean serum HDL cholesterol levels have fallen over the period. Coronary heart disease prevention and control programmes appear to have been successful in reducing the prevalence of most major coronary heart disease risk factors however some reorientation will be required to redress the adverse trends in HDL cholesterol levels and obesity.

Adult↗
PubMed1995

Association of angiotensinogen gene T235 variant with increased risk of coronary heart disease.

Several genes, including some encoding components of the renin angiotensin system, are associated with the risk of cardiovascular diseases. There have been reports linking a homozygous deletion allele of the angiotensin converting enzyme (ACE) gene (DD) with an increased risk of myocardial infarction, and some variants of the angiotensinogen gene with an increased risk of hypertension. In a case-control study of a caucasian population from New Zealand, we examined the associations with coronary heart disease (CHD) of ACE DD and of a mis-sense mutation with methionine to threonine aminoacid substitution at codon 235 in the angiotensinogen gene (T235). We studied 422 patients (mean age 62 years, 81% male) with documented CHD (50% with myocardial infarction) and 406 controls without known CHD (frequency-matched to cases by age and sex). Risk factors for CHD were assessed by standard questionnaire, physical examination, and blood tests. Genomic DNA from leucocytes was analysed for various ACE and angiotensinogen alleles. Angiotensinogen T235 homozygotes were at significantly increased risk of CHD generally (odds ratio 1.7, 2 p = 0.008) and of myocardial infarction specifically (1.8, 2 p = 0.009). Adjustment for several risk factors increased the estimate of CHD risk associated with this allele to 2.6 (2 p < 0.001) and the estimate for myocardial infarction risk to 3.4 (2 p < 0.001). By contrast, there was no evidence of a significant increase in the risk of CHD or myocardial infarction among individuals with ACE DD. We conclude that the T235 polymorphism of the angiotensinogen gene is an independent risk factor, which carries an approximately two-fold increased risk of CHD. In this study, however, ACE DD was not associated with any detectable increase in CHD risk.

Alleles↗
PubMed1995

Dual-acting thromboxane receptor antagonist/synthase inhibitors: synthesis and biological properties of [2-substituted-4-(3-pyridyl)-1,3-dioxan-5-yl] alkenoic acids.

The design, synthesis, and pharmacology of a new class of compounds possessing both thromboxane receptor antagonist and thromboxane synthase inhibitory properties are described. Replacement of the phenol group of the known thromboxane antagonist series 4(Z)-6-[(4RS,5SR)-4-(2-hydroxyphenyl)-1,3-dioxan-5-yl] hex-4-enoic acid by a 3-pyridyl group led to a series of compounds, 5, which were potent thromboxane synthase inhibitors and weak thromboxane antagonists. Further modifications at the dioxane C2 position led to compounds, 7, which were potent dual-acting agents. In the case of compound 7w, the dual activity was shown to reside almost exclusively in the (-)-enantiomer, 7x. Following oral dosing to rats and dogs, 7x (3 mg/kg) displayed significant dual activity over a period of at least 8 h.

Animals↗
PubMed1995

Effect of environmental factors on risk of injury of child pedestrians by motor vehicles: a case-control study.

OBJECTIVE: To identify and assess contribution of environmental risk factors for injury of child pedestrians by motor vehicles. DESIGN: Community based case-control study. Environmental characteristics of sites of child pedestrian injury were compared with the environmental characteristics of selected comparison sites. Each comparison site was the same distance and direction from home of control child as was the injury site from home or relevant case child. Two control sites were selected for each injury site. SETTING: Auckland region of New Zealand. SUBJECTS: Cases were 190 child pedestrians aged < 15 who were killed or hospitalised after collision with a motor vehicle on a public road during two years and two months. Controls were 380 children randomly sampled from population and frequency matched for age and sex. MAIN OUTCOME MEASURE: Traffic volume and speed and level of parking on curbs at injury sites and comparison sites. RESULTS: Risk of injury of child pedestrians was strongly associated with traffic volume: risk of injury at sites with highest traffic volumes was 14 times greater than that at least busy sites (odds ratio 14.30; 95% confidence interval 6.98 to 29.20), and risk increased with increasing traffic volume. High density of curb parking was also associated with increased risk (odds ratio 8.12; 3.32 to 19.90). Risk was increased at sites with mean speeds over 40 km/h (odds ratio 2.68; 1.26 to 5.69), although risk did not increase further with increasing speed. CONCLUSION: Reducing traffic volume in urban areas could significantly reduce rates of child pedestrian injury. Restricting curb parking may also be effective.

Accidents, Traffic↗
PubMed1995

End of the New Zealand asthma mortality epidemic.

In 1989, a case-control study reported that inhaled fenoterol was associated with the epidemic of asthma deaths that had affected New Zealand since 1976. The New Zealand Department of Health issued warnings about the safety of fenoterol and restricted its availability. The associated time trends are consistent with the hypothesis that fenoterol was the main factor in the New Zealand asthma mortality epidemic. The epidemic commenced when fenoterol was introduced in 1976, and the New Zealand death rate remained the highest in the world for more than a decade. After publication of the case-control study, the death rate fell by half and has now remained low for a further 3 years (1990-92). Time-trend data do not suggest a class effect of inhaled beta-agonists in the epidemic: there was no association between beta-agonist sales and the start of the epidemic, and total sales of inhaled beta-agonists actually increased slightly during 1989-90 when the epidemic came to an end. Time-trend data are also inconsistent with the hypothesis that the epidemic may have occurred because of underprescribing of inhaled corticosteroids. Similarly, time-trend data is incosistent with hypotheses postulating a major role of social factors such as unemployment. Data on time trends should be assessed with caution, because time trends in asthma deaths can be affected by many factors. Nevertheless, the New Zealand time trends are consistent with fenoterol being the main cause of the New Zealand asthma mortality epidemic and are inconsistent with a significant role for other suggested causes.

Administration, Inhalation↗
PubMed1995

Polymerase chain reaction for rapid detection of ocular adenovirus infection.

Adenoviruses are associated with endemic and epidemic acute conjunctivitis, large nosocomial outbreaks reflecting virus transmission on unwashed hands or inadequately sterilised ophthalmic instruments. The polymerase chain reaction (PCR) proved more sensitive than antigen detection by immune dot-blot test for the rapid diagnosis of ocular adenovirus infection (sensitivities in a retrospective study 112/123 (91%) versus 72/123 (59%), P < 0.001). Indeed, in a prospective comparison, DNA amplification and virus isolation generated similar numbers of positive results (34 versus 32), though five PCR positive results were possibly false positives. The sensitivity of the PCR was largely independent of adenovirus subgenus or serotype, though reduced sensitivity with subgenus B strains could not be excluded. Specimen preparation for DNA amplification using a simple lysis buffer proved more effective than phenol-chloroform extraction. The immune dot-blot test gave unavoidable false positive results, but with the PCR this problem could be minimized by technical modifications. The PCR could replace antigen detection and virus isolation as the initial test for adenoviruses in conjunctival swabs, with cell culture only being retained for adenovirus serotyping in PCR positive specimens and for other viruses such as herpes simplex.

Adenoviridae↗
PubMed1995

Potent inhibition of human immunodeficiency virus by MDL 101028, a novel sulphonic acid polymer.

MDL 101028, a novel biphenyl disulphonic acid urea co-polymer was designed and synthesised as a heparin mimetic. This low molecular weight polymer showed potent inhibition of human immunodeficiency virus type 1 (HIV-1) replication in a number of host-cell/virus systems, including primary clinical isolates of the virus cultured in human peripheral blood mononuclear cells (PBMCs). When compared with the heterogeneous polysulphated molecules, heparin and dextran sulphate, this chemically defined compound showed equivalent antiviral activity with 50% inhibitory concentrations (IC50s) in the range 0.27-3.0 micrograms/ml in the host-cell/virus systems tested. MDL 101028 also inhibited the replication of HIV type 2 and the simian immunodeficiency virus (SIV), as well as HIV-1 variants resistant to reverse transcriptase inhibitors. Virus growth was blocked when exposure of T-lymphocytes to MDL 101028 was restricted to the virus absorption stage, or even in whole blood conditions. MDL 101028 did not irreversibly inactivate virions, and in contrast to heparin, did not inhibit the attachment of radiolabelled HIV-1 to CD4+ T-cells. MDL 101028 blocked HIV-induced cell-to-cell fusion and this activity appears to explain the mechanism of its antiviral action. The antiviral evaluation of discrete oligomer molecules of MDL 101028 showed that a polymer chain length of six repeating units had optimal potency. The lack of anticoagulant properties and significant antiviral activity in whole blood may allow the development of MDL 101028 as a treatment of HIV infections.

Animals↗
PubMed1995

Naturally occurring tuberculosis caused by Mycobacterium bovis in brushtail possums (Trichosurus vulpecula): I. An epidemiological analysis of lesion distribution.

Gross and microscopic lesion distributions and culture test results are described for 73 tuberculous possums recovered from a series of cross-sectional studies involving about 500 detailed necropsies. Pathological findings from 11 terminally ill tuberculous possums are also described. Quantitative epidemiological techniques were applied to lesion site data to assess factors influencing the pathogenesis of the disease. In possums with gross lesions, the number of distinct body sites affected varied from one to 10 per animal, with a mean of 4.6. The total number of gross plus microscopic lesions varied from one to 28 per animal with a mean of 11.6, indicating that the degree of generalisation of disease was much greater than appeared grossly. Of 119 possums with no gross lesions which were subjected to additional examinations, tuberculosis was diagnosed in ten (8.4%) by histology or culture of pooled lymph nodes. Among cross-sectional sample tuberculous possums, lesions were found in lungs in 85%, in axillary lymphocentres in 85%, in inguinal lymphocentres in 69%, and in either axillary or inguinal lymphocentres in 95%, indicating that the disease spread rapidly to multiple body sites. More males than females were infected (relative risk = 1.78). When cross-sectionally sampled infected and non-infected possums were compared, no significant associations were found between the presence/absence of disease and either age or indices of body condition, although debility was seen in animals with terminal illness.

Journal Article↗