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Biomedical subjects

Michael J Stewart

Publications and source records attributed to Michael J Stewart.

27 records · Page 2Linked to original sources
PubMed2003

PKR's protective role in viral myocarditis.

Reovirus-induced murine myocarditis provides an excellent model for the human disease. Previously, we showed that reovirus induction of and sensitivity to interferon-beta (IFN-beta) are important determinants of protection against cardiac damage. IFN-beta induces a number of genes with antiviral activities, including the dsRNA-activated protein kinase, PKR. Once bound to viral dsRNA, PKR becomes activated and phosphorylates eukaryotic initiation factor-2 alpha (eIF2 alpha) leading to the cessation of host cell translation. Additionally, activated PKR can exert its antiviral effects by inducing phosphorylation of I kappa B, leading to the activation of the transcription factor NF kappa B and subsequent induction of IFN-beta. Thus, activated PKR can both induce and be induced by IFN-beta. Recently, numerous reports have shown PKR to be dispensable for both induction of IFN as well as protection against disease. However, both PKR's role in the heart in response to viral infection and its ability to prevent cardiac damage have gone largely unexplored. Here, we demonstrate PKR to be critical for viral induction of IFN-beta in primary cardiac myocyte cultures. Additionally, we show that loss of PKR leads to an increase in virulence for both myocarditic and nonmyocarditic reoviruses. Finally, we demonstrate PKR to be critical for protection against reovirus-induced viral myocarditis.

Animals↗
PubMed2003

Structural characterization of chromone C-glucosides in a toxic herbal remedy.

Two novel compounds, 8-C-D-glucopyranosyl-7-hydroxy-5-methylchromone-2-carboxylic acid and a 2-O'-p-coumaroyl derivative thereof, were identified in a herbal tea that caused severe vomiting in a South African patient who had taken the traditional remedy to clean his stomach. For structural characterization, electrospray (ES) ionization in combination with collision-induced dissociation (CID) and tandem mass spectrometry (MS/MS) were used, as well as UV and nuclear magnetic resonance (NMR) spectroscopy. Specific ions or neutral losses generated under conditions of ES-MS/CID/MS permitted the establishment of structural features such as the free carboxyl group, the C-hexosidic part and the p-coumaroyl group. NMR spectroscopy was necessary to support the structure of the chromone-type aglycone and the glucosidic parts. Since the compounds are structurally related to aloesin and aloeresin A, which are chemotaxonomic markers of Aloe species, and have not been previously reported, we propose that they were formed by oxidative degradation during preparation of the herbal tea from an Aloe species or during its storage.

Chromatography, High Pressure Liquid↗
PubMed2002

A severe case of multiple metal poisoning in a child treated with a traditional medicine.

A child who had been treated orally with a traditional medicine was admitted to hospital with diarrhoea, vomiting and severe metabolic acidosis. Following treatment for renal failure and supportive therapy, the child was discharged well. Analysis of the traditional remedy, a black powder, using inductively coupled plasma-optical emission revealed very high concentrations of iron and manganese. Other metals were also present at lesser, but still high concentrations. The composition suggested that this was a sample obtained from a surface fracture in Transvaal dolomite. Metal poisoning is not uncommon following the use of non-herbal traditional remedies in South Africa, but in this case the mixture appears to have been a combination of many metals and salts.

Humans↗
PubMed2002

Interferon regulatory factor-1, interferon-beta, and reovirus-induced myocarditis.

Viral myocarditis is an important human disease, and reovirus-induced myocarditis in mice provides an excellent model to study direct viral damage to the heart. Previously, we showed that reovirus induction of and sensitivity to interferon-beta (IFN-beta) is an important determinant of viral pathogenicity in the heart and that the transcription factor interferon regulatory factor-3 (IRF-3) is required for reovirus induction of IFN-beta in primary cardiac myocyte cultures. Given several lines of evidence suggesting a possible distinctive environment for IRFs in the heart, we have now focused on IRF-1. Previous studies demonstrated that viruses, double-stranded-RNA (dsRNA), and IFN-alpha/beta can each induce IRF-1 and that IRF-1 plays a role in dsRNA, but perhaps not viral, induction of IFN-alpha/beta. Importantly, none of these studies used a virus with a dsRNA genome (such as reovirus), none of them used a highly differentiated nonlymphoid cell type, and none of them addressed whether viral induction of IRF-1 is direct or is mediated through viral induction of IFN-beta. Indeed, as recently as this year it has been assumed that viral induction of IRF-1 is direct. Here, we found that reovirus induced IRF-1 in primary cardiac myocyte cultures, but that IRF-1 was not required for reovirus induction of IFN-beta. Surprisingly, we found that reovirus failed to induce IRF-1 in the absence of the IFN-alpha/beta response. This provides the first evidence that viruses may not induce IRF-1 directly. Finally, nonmyocarditic reovirus strains induced more cardiac lesions in mice deficient for IRF-1 than they did in wildtype mice, directly demonstrating a protective role for IRF-1. Together, the results indicate that while IRF-1 is downstream of the IFN-beta response, it plays an important protective role against viral myocarditis.

Animals↗
PubMed2002

South Africa: a toxicologist's goldmine.

The emerging nation of South Africa, in common with some other countries, notably Eastern Europe, is heir to decades of neglect with regards to the exposure of the majority of its population to toxic materials. In this short review, the major toxic health hazards are described. For most of these risks there are now programs in place to improve the situation, but co-ordination and financial constraints, along with the fact that the majority of the population neither live, nor work, in a controlled environment, mean that much remains to be done. The recent formation of a South African Toxicology society, which strives to bring together environmental, industrial, forensic and clinical toxicology should assist in an improvement, both in the epidemiology of toxicity in South Africa and in improved measures to reduce the incidence of preventable noncommunicable diseases related to both acute and chronic exposure to toxins. The South African scene also provides a "window' of opportunity to study the more fundamental aspects of exposure in human subjects and to couple these to animal and in vitro studies to elucidate the underlying mechanisms where these are unknown.

Animals↗
PubMed2002

Septic pulmonary emboli caused by a hemodialysis catheter.

We present an unusual complication caused by a dialysis catheter inserted through the internal jugular vein into the central venous system. The 49-year-old male patient developed a right atrial thrombus, which became infected with Staphylococcus aureus, resulting in septic pulmonary embolism and septicemic shock. The thrombus was excised on cardiopulmonary bypass. The patient made an uneventful recovery.

Catheterization↗