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Biomedical subjects

M Kennedy

Publications and source records attributed to M Kennedy.

At least 19 recordsLinked to original sources
PubMed2000

Use of a ground beef model to assess the effect of the lactoperoxidase system on the growth of Escherichia coli O157:H7, Listeria monocytogenes and Staphylococcus aureus in red meat.

The ability to preserve food in a state that is both appetising and nutritious is a basic requirement for health. Food poisoning represents a major source of illness and loss of productivity in many developed countries. Of particular concern in recent years are outbreaks of food poisoning associated with Escherichia coli O157:H7 or Listeria monocytogenes, many of which have been associated with the consumption of ground meat. Many of the chemicals presently licensed for use as food preservatives are increasingly being questioned with regard to their effects on humans, creating pressure on food suppliers to consider the use of 'natural' alternatives to these chemical agents. The potential use of one such agent, the lactoperoxidase system (LPS), for use in ground meat preparations is examined in this study. The degree of inhibition of growth of E. coli O157:H7, L. monocytogenes L45 and S. aureus R37 by LPS was examined in a broth system at 37 degrees C and in a ground beef system at 0, 6 and 12 degrees C. The degree of inhibition by LPS of natural populations of microorganisms present in ground beef obtained from eight retail outlets and incubated at room temperature was also examined. For each of the strains examined, sensitivity from most to least sensitive followed the order L. monocytogenes L45, S. aureus R37 and E. coli O157:H7. In each case the ability of LPS to inhibit growth was highly temperature dependent and maximal at a temperature permissive but not optimal for growth of the test strain. The numbers of bacteria detected in ground beef obtained from retail outlets varied considerably between the eight samples. In all cases, numbers of bacteria increased markedly in the uninhibited control over the 4 h incubation time and, with the exception of one faecal coliform count, growth of the microbial populations was strongly inhibited by the presence of LPS. It was concluded that LPS could potentially be applied to a considerably wider range of food products than those to which it is presently restricted.

Animals↗
PubMed2000

Emergence of dual resistance to zidovudine and lamivudine in HIV-1-infected patients treated with zidovudine plus lamivudine as initial therapy.

Presence of mutations associated with resistance to zidovudine or lamivudine was determined in isolates of HIV-1 obtained after long-term follow-up of 64 infected individuals who received zidovudine, lamivudine, or both drugs as initial antiretroviral therapy. Zidovudine resistance mutations were less frequent in isolates from patients treated with combination lamivudine plus zidovudine compared with zidovudine alone, but these mutations accumulated over time. Phenotypic resistance to both drugs was found in isolates from 3 of 23 patients. In 3 other patients, lamivudine-resistant virus detected at week 12 was replaced by wild-type virus after longer follow-up, which correlated with a return to baseline levels of plasma HIV-1 RNA. These results show that dual resistance to zidovudine and lamivudine develops over time despite the delayed emergence of zidovudine-resistant mutations. These results also suggest a selective advantage in vivo for HIV-1 species that are wild-type at RT codon 184.

Amino Acid Sequence↗
PubMed2000

Estimation of the oxalate content of foods and daily oxalate intake.

BACKGROUND: The amount of oxalate ingested may be an important risk factor in the development of idiopathic calcium oxalate nephrolithiasis. Reliable food tables listing the oxalate content of foods are currently not available. The aim of this research was to develop an accurate and reliable method to measure the food content of oxalate. METHODS: Capillary electrophoresis (CE) and ion chromatography (IC) were compared as direct techniques for the estimation of the oxalate content of foods. Foods were thoroughly homogenized in acid, heat extracted, and clarified by centrifugation and filtration before dilution in water for analysis. Five individuals consuming self-selected diets maintained food records for three days to determine their mean daily oxalate intakes. RESULTS: Both techniques were capable of adequately measuring the oxalate in foods with a significant oxalate content. With foods of very low oxalate content (<1.8 mg/100 g), IC was more reliable than CE. The mean daily intake of oxalate by the five individuals tested was 152 +/- 83 mg, ranging from 44 to 352 mg/day. CONCLUSIONS: CE appears to be the method of choice over IC for estimating the oxalate content of foods with a medium (>10 mg/100 g) to high oxalate content due to a faster analysis time and lower running costs, whereas IC may be better suited for the analysis of foods with a low oxalate content. Accurate estimates of the oxalate content of foods should permit the role of dietary oxalate in urinary oxalate excretion and stone formation to be clarified. Other factors, apart from the amount of oxalate ingested, appear to exert a major influence over the amount of oxalate excreted in the urine.

Adult↗
PubMed2000

Localisation of HHV-8 in AIDS related lymphadenopathy.

BACKGROUND: Many lymph node abnormalities have been described in AIDS. These include opportunistic infections that sometimes result in spindle cell pseudotumours, Kaposi's sarcoma (KS), malignant lymphoma (Hodgkin's and non-Hodgkin's), and florid reactive hyperplasia. Among these, reactive hyperplasia is the most common manifestation of AIDS related lymphadenopathy. AIM: To examine whether human herpesvirus 8 (HHV-8), the aetiological agent of KS, can be localised in AIDS related lymphadenopathy and whether its appearance in such nodes is predictive of Kaposi's sarcoma development. METHODS: A series of human immunodeficiency virus (HIV) positive men (n = 21) with AIDS related lymphadenopathy who at the time of presentation had KS or subsequently developed KS (n = 5) were examined. The prevalence of HHV-8 was assessed in these patients using solution phase polymerase chain reaction (PCR), real time TaqMan quantitative PCR, and in cell amplification techniques (PCR in situ hybridisation (PCR-ISH) and labelled primer driven in cell amplification). RESULTS: Using standard solution phase PCR in a nested format, only two of the 21 patients with AIDS related lymphadenopathy were positive for HHV-8. The lymph node of one of these patients contained KS lesions. Three HHV-8 positive patients were identified using TaqMan PCR (the original two positive patients and one additional patient). All of the positive patients either subsequently developed KS (n = 2) or had KS at the time of diagnosis (n = 1). Two additional patients subsequently developed KS, but were negative for HHV-8 by solution phase PCR and TaqMan PCR. Using PCR-ISH, HHV-8 amplicons were identified in some lymphoid cells (in one patient) and in spindle cells of the KS lesion in another. The positive lymphoid cells were predominantly concentrated in B cell areas of the affected lymph nodes, confirming the B cell tropism exhibited by HHV-8. CONCLUSIONS: The presence of HHV-8 in AIDS related lymphadenopathy is predictive of KS development and probably represents seeding of HHV-8 infected B cells from the peripheral blood. These findings support a role for HHV-8 in the pathobiology of KS.

AIDS-Related Complex↗
PubMed2000

Cellular localisation of HHV-8 in Castleman's disease: is there a link with lymph node vascularity?

AIMS: Human herpesvirus 8 (HHV-8) has been identified in multicentric Castleman's disease and in angioimmunoblastic lymphadenopathies. However, the presence of the virus does not necessarily indicate an aetiological role in these conditions. This study investigates the cell types infected by HHV-8 in Castleman's disease and examines the correlation between HHV-8 and Castleman's disease lymph node angiogenesis. METHODS: Sixteen formalin fixed, paraffin wax embedded samples from patients with Castleman's disease (six multicentric, 10 solitary) were examined for the presence of HHV-8 using the polymerase chain reaction (PCR), non-isotopic in situ hybridisation, PCR in situ hybridisation (PCR-ISH), and real time quantitative TaqMan PCR to HHV-8 open reading frame 26 (ORF-26), and viral (v)-cyclin encoding regions. Vascularity was assessed using CD34, CD31, and factor VIII immunocytochemistry, and lymph nodes were scored as "low" or "high". RESULTS: Five multicentric Castleman's disease and two solitary Castleman's disease biopsies were positive for HHV-8. HHV-8 was identified in approximately 10% of intranodal B lymphocytes, in endothelial cells, and in subcapsular spindle cell proliferations. The copy number of HHV-8 was low at 10-50 copies/1000 cells. The highest copy number was in subcapsular spindle cells. There was no correlation between vascularity score and HHV-8 status. CONCLUSION: The preferential localisation of HHV-8 in subcapsular spindle cell proliferations (where early intranodal Kaposi's sarcoma initiates) and endothelial cells in Castleman's disease might finally explain the link between intranodal Kaposi's sarcoma and Castleman's disease.

Adult↗
PubMed2000

A transitional stage in the commitment of mesoderm to hematopoiesis requiring the transcription factor SCL/tal-1.

In this report, we describe the identification and characterization of an early embryoid body-derived colony, termed the transitional colony, which contains cell populations undergoing the commitment of mesoderm to the hematopoietic and endothelial lineages. Analysis of individual transitional colonies indicated that they express Brachyury as well as flk-1, SCL/tal-1, GATA-1, (beta)H1 and (beta)major reflecting the combination of mesodermal, hematopoietic and endothelial populations. This pattern differs from that found in the previously described hemangioblast-derived blast cell colonies in that they typically lacked Brachyury expression, consistent with their post-mesodermal stage of development (Kennedy, M., Firpo, M., Choi, K., Wall, C., Robertson, S., Kabrun, N. and Keller, G. (1997) Nature 386, 488-493). Replating studies demonstrated that transitional colonies contain low numbers of primitive erythroid precursors as well as a subset of precursors associated with early stage definitive hematopoiesis. Blast cell colonies contain higher numbers and a broader spectrum of definitive precursors than found in the transitional colonies. ES cells homozygous null for the SCL/tal-1 gene, a transcription factor known to be essential for development of the primitive and definitive hematopoietic systems, were not able to form blast colonies but did form transitional colonies. Together these findings suggest that the transitional colony represents a stage of development earlier than the blast cell colony and one that uniquely defines the requirement for a functional SCL/tal-1 gene for the progression to hematopoietic commitment.

Animals↗
PubMed1999

Tuberculosis in immigrants and visitors.

Immigrants and visitors are a significant factor in the epidemiology of tuberculosis (TB) in New Zealand, accounting for an increasing proportion of notifications in recent years. At present screening of immigrants from countries with a high incidence of TB is inadequate. There are deficiencies in procedures, inadequate screening coverage, ineffectual coordination between the Ministry of Health and New Zealand Immigration Service, incomplete follow-up on those at risk of TB, confusion over financial responsibility, inadequate data to describe the problems and monitor interventions, and a lack of commitment to assistance with TB control in neighbouring countries from which some of our TB arises. We make recommendations in all of these areas. Timely screening of high-risk immigrants should be seen as health protection for ethnic minorities.

Emigration and Immigration↗
PubMed1999

Hematopoietic commitment during embryogenesis.

Hematopoiesis develops initially as discrete blood islands in the extraembryonic yolk sac of the embryo. These blood islands consist of clusters of primitive erythrocytes surrounded by developing angioblasts that ultimately form the yolk sac vasculature. The close developmental association of these early hematopoietic and endothelial cells has led to the hypothesis that they develop from a common precursor, a cell known as the hemangioblast. Using a developmental model system based on the in vitro differentiation capacity of embyronic stem (ES) cells, we have identified a precursor with the capacity to generate endothelial as well as primitive and definitive hematopoietic progeny. The developmental potential of this precursor population suggests that it represents the in vitro equivalent of the hemangioblast.

Animals↗
PubMed1999

Structure, G protein activation, and functional relevance of the cardiac G protein-gated K+ channel, IKACh.

The muscarinic-gated atrial potassium channel IKACh has been well characterized functionally, and has been an excellent model system for studying G protein/effector interactions. Complementary DNAs encoding the composite subunits of IKACh have been identified, allowing direct probing of structural and functional features of the channel. Here, we highlight recent approaches taken in our laboratory to determine the oligomeric structure of native cardiac IKACh, the mechanism of activation of IKACh by G proteins, and the relevance of IKACh to cardiac physiology.

Amino Acid Sequence↗
PubMed1999

The long and short of it: branch lengths and the problem of placing the New Zealand short-tailed bat, Mystacina.

The taxonomic position of the endemic New Zealand bat genus Mystacina has vexed systematists ever since its erection in 1843. Over the years the genus has been linked with many microchiropteran families and superfamilies. Most recent classifications place it in the Vespertilionoidea, although some immunological evidence links it with the Noctilionoidea (=Phyllostomoidea). We have sequenced 402 bp of the mitochondrial cytochrome b gene for M. tuberculata (Gray in Dieffenbach, 1843), and using both our own and published DNA sequences for taxa in both superfamilies, we applied different tree reconstruction methods to find the appropriate phylogeny and different methods of estimating confidence in the parts of the tree. All methods strongly support the classification of Mystacina in the Noctilionoidea. Spectral analysis suggests that parsimony analysis may be misleading for Mystacina's precise placement within the Noctilionoidea because of its long terminal branch. Analyses not susceptible to long-branch attraction suggest that the Mystacinidae is a sister family to the Phyllostomidae. Dating the divergence times between the different taxa suggests that the extant chiropteran families radiated around and shortly after the Cretaceous-Tertiary boundary. We discuss the biogeographical implications of classifying Mystacina within the Noctilionoidea and contrast our result with those classifications placing Mystacina in the Vespertilionoidea, concluding that evidence for the latter is weak.

Animals↗
PubMed1999

The cost of elective and emergency repair of AAA in patients under and over the age of 80.

BACKGROUND: As Australia's population ages, the number of elderly patients presenting for surgery of abdominal aortic aneurysms (AAA), both elective and ruptured, will increase. The aim of the present study was to compare the costs of treatment of patients with AAA, under and over the age of 80, in the elective and emergency settings in a hospital with a divisional structure in which the true costs can be accurately obtained. METHODS: A total of 40 patients were selected at random from a series of 267 patients treated with open surgery for AAA between January 1987 and December 1994, 10 in each of four groups: group A, elective repair in patients aged < 80 (171/267); group B, elective AAA repair in patients aged > 80 (25/267); group C, emergency AAA repair in patients aged < 80 (50/267); and group D, emergency AAA repair in patients aged > 80 (11/267). A retrospective analysis of the hospital costs of treatment of these patients at St George Hospital was conducted. These true costs were then compared to Australian National Diagnostic Related Group (AN-DRG) costs. RESULTS: Group A and B had no mortality. In Group C and D the mortality was 20 and 60%, respectively. The emergency treatment groups also had longer lengths of stay. A statistically significant difference in cost of AAA repair between elective and emergency groups in both age groups was seen; that is, group A cost less than group C and group B cost less than group D. Costs per survivor, however, showed a dramatic difference between the cost of group C patients ($30000) and group D patients ($60000). In comparison with AN-DRG calculated costs, the true costs of groups A and B were equivalent to AN-DRG costs. In the emergency groups, however, there were marked discrepancies between the true cost ($61000) and that calculated by the DRG ($25000) in group D, with similar differences seen in group C to a lesser extent. CONCLUSION: Emergency repair of AAA is significantly more expensive and has a high mortality in the over-80 age group. Also, there is a substantial shortfall between the true costs of treating these patients and the funds allocated for treatment in this group.

Aged↗
PubMed1999

Development of erythroid and myeloid progenitors in the yolk sac and embryo proper of the mouse.

In this study, we have mapped the onset of hematopoietic development in the mouse embryo using colony-forming progenitor assays and PCR-based gene expression analysis. With this approach, we demonstrate that commitment of embryonic cells to hematopoietic fates begins in proximal regions of the egg cylinder at the mid-primitive streak stage (E7.0) with the simultaneous appearance of primitive erythroid and macrophage progenitors. Development of these progenitors was associated with the expression of SCL/tal-1 and GATA-1, genes known to be involved in the development and maturation of the hematopoietic system. Kinetic analysis revealed the transient nature of the primitive erythroid lineage, as progenitors increased in number in the developing yolk sac until early somite-pair stages of development (E8.25) and then declined sharply to undetectable levels by 20 somite pairs (E9.0). Primitive erythroid progenitors were not detected in any other tissue at any stage of embryonic development. The early wave of primitive erythropoiesis was followed by the appearance of definitive erythroid progenitors (BFU-E) that were first detectable at 1-7 somite pairs (E8.25) exclusively within the yolk sac. The appearance of BFU-E was followed by the development of later stage definitive erythroid (CFU-E), mast cell and bipotential granulocyte/macrophage progenitors in the yolk sac. C-myb, a gene essential for definitive hematopoiesis, was expressed at low levels in the yolk sac just prior to and during the early development of these definitive erythroid progenitors. All hematopoietic activity was localized to the yolk sac until circulation was established (E8.5) at which time progenitors from all lineages were detected in the bloodstream and subsequently in the fetal liver following its development. This pattern of development suggests that definitive hematopoietic progenitors arise in the yolk sac, migrate through the bloodstream and seed the fetal liver to rapidly initiate the first phase of intraembryonic hematopoiesis. Together, these findings demonstrate that commitment to hematopoietic fates begins in early gastrulation, that the yolk sac is the only site of primitive erythropoiesis and that the yolk sac serves as the first source of definitive hematopoietic progenitors during embryonic development.

Animals↗