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Biomedical subjects

M Stevenson

Publications and source records attributed to M Stevenson.

At least 109 records · Page 6Linked to original sources
PubMed1997

SH3-mediated Hck tyrosine kinase activation and fibroblast transformation by the Nef protein of HIV-1.

Tyrosine kinases of the Src family are regulated via their Src homology 2 (SH2) and SH3 domains. The Nef protein of human immunodeficiency virus-1 (HIV-1) has previously been shown to bind with high affinity and specificity in vitro to the SH3 domain of Hck, a Src family member expressed primarily in myeloid cells. However, the effect of Nef on Hck activity in living cells is unknown. Here we show that Rat-2 fibroblasts co-expressing Hck and Nef rapidly developed transformed foci, whereas control cells expressing either protein alone did not. Nef formed a stable complex with Hck and stimulated its tyrosine kinase activity in vivo. Mutagenesis of the Nef proline-rich motif essential for SH3 binding completely blocked complex formation, kinase activation, and transformation, indicating that the Nef SH3-binding function is required for its effects on Hck. These results provide direct evidence that SH3 engagement is sufficient to activate a Src family kinase in vivo and suggest that Hck may be activated by Nef in HIV-infected macrophages.

Animals↗
PubMed1997

Quantitative competitive RNA PCR for quantitation of virion-associated HIV-1 RNA.

Quantitative competitive PCR is a highly sensitive technique that allows accurate quantitation of small amounts of RNA. We have modified the original method to include the use of an internal standard at all stages of sample analysis. In this way, the method can accommodate for variations in the recovery of viral particles and in the isolation of genomic RNA as well as provide a suitable competitive substrate during quantitative RNA PCR. We have used this method to characterize changes in virus load in plasma of HIV-1-seropositive individuals following their vaccination against opportunistic infections.

Blotting, Southern↗
PubMed1997

Childhood pedestrian injuries: what can changes to the road environment achieve?

With the lack of any significant reduction in the mortality rates from pedestrian injury in Western Australia over the past decade, the need for efficacious prevention strategies is paramount. Using data from a case-control study of childhood pedestrian injuries, this study considered the effect on public health of an environmental initiative for prevention. Population-attributable risk proportions were calculated for the variables 'volume of traffic' and 'visual obstacles', which were found to predict the likelihood of pedestrian injury. The results suggest that 41 per cent (95 per cent confidence interval (CI) 13 to 62) of childhood pedestrian injuries can be attributed to volumes of traffic in excess of 10,000 vehicles per week, and 20 per cent (CI 11 to 48) of injuries can be attributed to visual obstacles on the street verge. It was also estimated that childhood pedestrian injuries could be reduced by up to 30 per cent if children's exposure to roads with volumes of traffic exceeding 10,000 vehicles per week, could be reduced to 15 per cent or less. Similarly, a reduction of up to 8 per cent could occur if visual obstacles on the roadside were reduced to 15 per cent. Changes to the road environment have potential to prevent injury to children.

Accidents, Traffic↗
PubMed1997

An international study of the exposure of children to traffic.

OBJECTIVES: To examine the extent of international differences in children's exposure to traffic as pedestrians or bicyclists. DESIGN: Children's travel patterns were surveyed using a parent-child administered questionnaire. Children were sampled via primary schools, using a probability cluster sampling design. SETTING: Six cities in five countries: Melbourne and Perth (Australia), Montreal (Canada), Auckland (New Zealand), Umeå (Sweden), and Baltimore (USA). SUBJECTS: Children aged 6 and 9 years. MAIN OUTCOME MEASURES: Modes of travel on the school-home journey, total daily time spent walking, and the average daily number of roads crossed. MAIN FINDINGS: Responses were obtained from the parents of 13423 children. There are distinct patterns of children's travel in the six cities studied. Children's travel in the three Australasian cities, Melbourne, Perth and Auckland, is characterised by high car use, low levels of bicycling, and a steep decline in walking with increasing car ownership. In these cities, over a third of the children sampled spent less than five minutes walking per day. In Montreal, walking and public transport were the most common modes of travel. In Umeå, walking and bicycling predominated, with very low use of motorised transport. In comparison with children in the Australasian and North American cities, children in Umeå spend more time walking, with 87% of children walking for more than five minutes per day. CONCLUSIONS: There are large international differences in the extent to which children walk and cycle. These findings would suggest that differences in 'exposure to risk' may be an important contributor to international differences in pedestrian injury rates. There are also substantial differences in pedestrian exposure to risk by levels of car ownership-differences that may explain socioeconomic differentials in pedestrian injury rates.

Australia↗
PubMed1997

The PRECEDE-PROCEED model: application to planning a child pedestrian injury prevention program.

OBJECTIVES: The objectives were first, to modify the PRECEDE-PROCEED model and to use it is as a basis for planning a three year intervention trial that aims to reduce injury to child pedestrians. A second objective was to assess the suitability of this process for planning such a relatively complex program. SETTING: The project was carried out in 47 primary schools in three local government areas, in the Perth metropolitan area. METHODS: The program was developed, based on extensive needs assessment incorporating formative evaluations. Epidemiological, psychosocial, environmental, educational, and demographic information was gathered, organised, and prioritised. The PRECEDE-PROCEED model was used to identify the relevant behavioural and environmental risk factors associated with child pedestrian injuries in the target areas. Modifiable causes of those behavioural and environmental factors were delineated. A description of how the model facilitated the development of program objectives and subobjectives which were linked to strategy objectives, and strategies is provided. RESULTS: The process used to plan the child pedestrian injury prevention program ensured that a critical assessment was undertaken of all the relevant epidemiological, behavioural, and environmental information. The gathering, organising, and prioritising of the information was facilitated by the process. CONCLUSIONS: The use of a model such as PRECEDE-PROCEED can enhance the development of a child injury prevention program. In particular, the process can facilitate the identification of appropriate objectives which in turn facilitates the development of suitable interventions and evaluation methods.

Accident Prevention↗
PubMed1997

Women with recurrent vaginal candidosis have normal peripheral blood B and T lymphocyte subset levels.

OBJECTIVE: To compare the B and T lymphocyte subset levels of otherwise healthy women suffering from frequently recurrent vaginal candidosis with a healthy control group. SUBJECTS: 26 unselected otherwise healthy women of reproductive age with at least four attacks of vaginal candidosis in the past year and more than three vaginal isolates of a moderate or heavy growth of Candida albicans. Controls were 26 patients or clinical and laboratory staff (asymptomatic for genital infection) matched for time of day and age within 5 years. Only three patients accepted an HIV test. All proved HIV negative. No controls were tested. MAIN OUTCOME MEASURES: T lymphocyte subsets (CD4 and 8) and B lymphocytes (CD 19) as estimated from the total lymphocyte count and flow cytometry. RESULTS: No statistically significant difference between patients and controls. CONCLUSION: No significant difference was found between patients and controls in levels of lymphocyte subsets.

Adult↗
PubMed1996

Nuclear import and cell cycle arrest functions of the HIV-1 Vpr protein are encoded by two separate genes in HIV-2/SIV(SM).

The vpr genes of human and simian immunodeficiency viruses (HIV/SIV) encode proteins which are packaged in the virus particle. HIV-1 Vpr has been shown to mediate the nuclear import of viral reverse transcription complexes in non-dividing target cells (e.g. terminally differentiated macrophages), and to alter the cell cycle and proliferation status of the infected host cell. Members of the HIV-2/SIV(SM) group encode, in addition to Vpr, a related protein called Vpx. Because these two proteins share considerable sequence similarity, it has been assumed that they also exhibit similar functions. Here, we report that the functions of Vpr and Vpx are distinct and non-redundant, although both proteins are components of the HIV-2/SIV(SM) virion and reverse transcription complex. Characterizing SIV(SM) proviruses defective in one or both genes, we found that Vpx is both necessary and sufficient for the nuclear import of the viral reverse transcription complex. In contrast, Vpr, but not Vpx, inhibited the progression of infected host cells from the G2 to the M phase of the cell cycle. Thus, two independent functions of the HIV-1 Vpr protein are encoded by separate genes in HIV-2/SIV(SM). This segregation is consistent with the conservation of these genes in HIV-2/SIV(SM) evolution, and underscores the importance of both nuclear transport and cell cycle arrest functions in primate lentivirus biology.

Animals↗
PubMed1996

Evidence for load-dependent and load-independent determinants of cardiac natriuretic peptide production.

BACKGROUND: In hypertension with cardiac hypertrophy, the specific contributions to increased production of the cardiac natriuretic peptides (NP) atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) by load and the hypertrophic process are not known. In the present work we determine ANF and BNP synthesis and secretion in the aortic-banded rat treated with dosage schedules of the ACE inhibitor ramipril that result in the prevention or regression of both hypertension and hypertrophy (high dosage) or in the prevention or regression of hypertrophy alone with persistent hypertension (low dosage). Myosin heavy chain (MHC) isoform switch was studied as an indicator of ventricular cardiocyte hypertrophy as well as the levels of collagen III mRNA as a measure of changes in extracellular matrix. METHODS AND RESULTS: Ramipril was administered for 6 weeks just after suprarenal aortic banding, or rats were banded for 6 weeks, after which ramipril was administered during the following 6 weeks. Banding caused an increase in blood pressure, left ventricular weight-to-body weight ratio, plasma and ventricular NP, ventricular NP mRNA, collagen III, and beta-MHC mRNA. Ramipril at 1 mg/kg normalized all these parameters while ramipril at 10 micrograms/kg normalized left ventricular weight-to-body weight ratio but not blood pressure. Plasma and ventricular NP content and mRNA levels were partially normalized by ramipril (10 micrograms/kg). Ramipril (10 micrograms/kg) prevented increased collagen III mRNA levels but did not affect beta-MHC mRNA levels. CONCLUSIONS: (1) NP production and secretion in aortic-banded rats are independently related to increased blood pressure and hypertrophy. (2) A load-dependent component is more important than a load-independent component in regulating left ventricular NP production. (3) ANF production is more sensitive than BNP production to the load-independent component. (4) Low-dose ramipril treatment reverses hypertrophy and the increased collagen III expression but does not reverse the increased beta-MHC isoform expression, suggesting that these are independently regulated processes. (5) Aortic banding and ACE inhibition do not affect atrial NP production and content.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Phosphorylation-dependent human immunodeficiency virus type 1 infection and nuclear targeting of viral DNA.

In the replication of human immunodeficiency virus type 1 (HIV-1), gag MA (matrix), a major structural protein of the virus, carries out opposing targeting functions. During virus assembly, gag MA is cotranslationally myristoylated, a modification required for membrane targeting of gag polyproteins. During virus infection, however, gag MA, by virtue of a nuclear targeting signal at its N terminus, facilitates the nuclear localization of viral DNA and establishment of the provirus. We now show that phosphorylation of gag MA on tyrosine and serine prior to and during virus infection facilitates its dissociation from the membrane, thus allowing it to translocate to the nucleus. Inhibition of gag MA phosphorylation either on tyrosine or on serine prevents gag MA-mediated nuclear targeting of viral nucleic acids and impairs virus infectivity. The requirement for gag MA phosphorylation in virus infection is underscored by our finding that a serine/threonine kinase is associated with virions of HIV-1. These results reveal a novel level of regulation of primate lentivirus infectivity.

Base Sequence↗
PubMed1996

Portals of entry: uncovering HIV nuclear transport pathways.

The ability to infect non-dividing cells sets aside lentiviruses such as HIM from the animal onco-retroviruses which are only able to infect actively dividing cells. This difference in lentivirus and oncovirus biology can be attributed to the relative ability of the reverse transcription complex (preintegration complex) of the virus to enter the nucleus. For lentiviruses such as HIV, active transport processes facilitate this translocation. By contrast, nuclear membrane breakdown at mitosis is required before the reverse transcription complex o f onco-retroviruses can enter the nucleus. Several components o f the HIV reverse transcription complex that facilitate its nuclear transport have now been identified and an analysis o f these import factors is yielding insight into how opposing targeting functions o f viral proteins are regulated.

Journal Article↗
PubMed1996

Mass in the post nasal space and acquired immune deficiency syndrome.

We report a case of previously undiagnosed acquired immunodeficiency syndrome (AIDS) who had a mass in the post-nasal space causing almost complete nasal obstruction. Histology showed both respiratory and squamous epithelium covering an active chronic inflammatory infiltrate. Lymphoma, Kaposi's sarcoma and infiltrative fungal sinusitis were excluded. There was no evidence of the common viruses associated with lesions in AIDS. Unlike adenoid hypertrophy, the lesion was an exuberant growth with an additional chronic inflammatory reaction due to ulceration of the surface epithelium.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Chewing as a social act: cultural displacement and khat consumption in the East African communities of Melbourne.

In this paper we present a review of practices surrounding the consumption of khat (Catha edulis) within recent migrant communities in Melbourne from East Africa. Cultures in East Africa and the Arabian Peninsular have used khat as a stimulant since the seventh century and the practice of coming together to chew the leaves of the khat plant has acquired unique cultural importance. Based on focus-group interviews the research examines transformations taking place in the meaning of khat for East African communities within their experiences of displacement and considers how the arrival of khat might be managed in the Australian context. Emphasis is given to indigenous models and the cultural context of practices surrounding khat. This anthropology of khat use in Melbourne summarizes issues such as who chews it, traditional settings for khat gatherings, culturally defined effects of the leaf, health effects, beliefs and attitudes, levels of use, gendered attitudes and questions of dependence. These issues raise questions regarding the reception of indigenous substance use within a state that claims to be multicultural.

Journal Article↗
PubMed1996

Regulation and characterization of the interferon-alpha present in patients with advanced human immunodeficiency virus type 1 disease.

To examine a possible association between plasma viremia and interferon-alpha (IFN-alpha) in patients with the acquired immunodeficiency syndrome (AIDS), we performed IFN plasma immunoadsorption by apheresis (IFN-alpha apheresis) in four volunteers with AIDS who had sustained levels of endogenous plasma IFN-alpha. IFN-alpha apheresis with two plasma volume exchanges was performed daily for 5 days. Clinical signs and symptoms and hematologic, virologic, and immunologic parameters were monitored. Two subjects developed anemia from phlebotomy, and one had a catheter++-associated bacteremia. The IFN-alpha apheresis was effective only in transiently removing IFN-alpha: depletion of IFN-alpha led only to its rapid reconstitution. Cell-associated HIV-1 was unchanged, but three of four subjects had a modest decrease in culturable plasma virus burden following the procedures. The recovery of in vivo HIV-1-related IFN-alpha by apheresis allowed its biologic and biochemical characterization. The HIV-1 IFN-alpha showed characteristics on ELISA, western blot, and biologic assays similar to two subspecies of the natural protein. The natural, recombinant, and HIV-1-induced IFN-alpha s demonstrated nearly identical antiviral activities. The HIV-1 IFN-alpha eluted from the column was not acid labile. The inability of large amounts of plasma IFN-alpha found in some patients with AIDS to affect viral burden likely reflects properties of the virus or of host factors independent of IFN-alpha.

Acquired Immunodeficiency Syndrome↗