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Biomedical subjects

S Stewart

Publications and source records attributed to S Stewart.

At least 73 records · Page 4Linked to original sources
PubMed2001

Anti-GQ1b ganglioside antibodies mediate complement-dependent destruction of the motor nerve terminal.

Miller-Fisher syndrome is an autoimmune neuropathy characterized by ataxia, areflexia and ophthalmoplegia, and in the majority of cases the presence of high titres of anti-GQ1b ganglioside antibodies. In an ex vivo model, human and mouse anti-GQ1b antibodies have been shown previously to induce a complement-dependent alpha-latrotoxin-like effect on the murine motor endplate, i.e. they bring about massive quantal release of acetylcholine and eventually block neuromuscular transmission. Using immunofluorescence microscopy with image analysis, we show here that the late stages of this electrophysiological effect temporally coincide with the loss of heavy neurofilament (200 kDa) and type III beta-tubulin immunostaining and structural breakdown of the nerve terminal, as demonstrated by electron microscopy. Ultrastructurally, axon terminals were disorganized, depleted of vesicles, and subdivided by the infiltrating processes of capping Schwann cells. These findings provide clear pathological evidence to support a role for anti-ganglioside antibodies in mediating nerve terminal injury and further advance the view that this site may be of importance as a target in some human neuropathies.

Alkaline Phosphatase↗
PubMed2001

Addressing the burden of heart failure in Australia: the scope for home-based interventions.

The growing burden of heart failure (HF) challenges health practitioners to implement and evaluate models of care to facilitate optimal health related outcomes. Australia supports a publicly funded universal health insurance system with a strong emphasis on primary care provided by general practitioners. The burden of chronic HF, and a social and political framework favoring community-based, noninstitutionalized care, represents an ideal environment in which home-based HF programs can be implemented successfully. Cardiovascular nurses are well positioned to champion and mentor implementation of evidence-based, patient-centered programs in Australian communities. This paper describes the facilitators and barriers to implementation of best practice models in the Australian context. These include the challenge of providing care in a diverse, multicultural society and the need for clinical governance structures to ensure equal access to the most effective models of care.

Aged↗
PubMed2001

Research in cardiovascular nursing in Europe: toward a UNITED approach. Undertaking Nursing Interventions Throughout Europe Research Group.

This article describes the efforts of a recent initiative of the Working Group on Cardiovascular Nursing of the European Society of Cardiology. The Undertaking Nursing Interventions Throughout Europe (UNITE) Research Group represents a truly international team of nurses who collaborate on a number of research studies. The major focus of the group is to provide better care to patients in whom modern day treatment has proven to be ineffectual such as patients with chronic, intractable angina.

Cardiovascular Diseases↗
PubMed2001

The natural course of hepatitis C virus infection after 22 years in a unique homogenous cohort: spontaneous viral clearance and chronic HCV infection.

BACKGROUND/AIMS: The cohort of Irish women infected with hepatitis C virus (HCV) genotype 1b via contaminated anti-D immunoglobulin in 1977 represent a unique homogenous group to investigate the natural course of HCV infection. METHODS: The clinical status of 87 polymerase chain reaction (PCR) positive and 68 PCR negative women was investigated at diagnosis (1994/95) and after 4-5 years of follow up (21/22 years after inoculation). Other features investigated included: histological status/progression, psychosocial impact of HCV infection, extrahepatic manifestations, and HLA class II associations. RESULTS: The most common symptoms reported were fatigue and arthralgia. Furthermore, 77% of women fell within the clinical range for psychological distress. A history of icteric hepatitis was reported in 20.6% of PCR negative and 3.4% of PCR positive women after inoculation (p=0.002). The mean histological activity index/fibrosis scores of PCR positive and negative women were 4.1 (1.4)/1.1 (1.3) and 2.1 (1.5)/0.15 (0.36) at diagnosis and 4.1 (1.2)/1.0 (1.0) in 44 PCR positive women after five years of follow up. Cirrhosis or hepatocellular carcinoma was not observed. The DRB1*01 allele was present in 28.8% of PCR negative and 8.7% of PCR positive women (p=0.004). The prevalence rates of mixed cryoglobulinaemia, sicca complex, positive thyroid autoantibodies, antinuclear antibody, rheumatoid factor, and antimitochondrial antibody in PCR positive women were 12.7%, 7.6%, 13.9%, 5.1%, 3.8%, and 3.8%. CONCLUSIONS: A benign course of HCV infection with lack of disease progression was observed in women with chronic HCV, 22 years after inoculation. Acute icteric hepatitis and the HLA DRB1*01 allele were associated with viral clearance. Despite this favourable outcome, high levels of psychological distress and poor quality of life were present.

Alanine Transaminase↗
PubMed2001

Population prevalence, incidence, and predictors of atrial fibrillation in the Renfrew/Paisley study.

OBJECTIVES: Though atrial fibrillation (AF) is an important cause of cardiovascular morbidity, there are few large epidemiological studies of its prevalence, incidence, and risk factors. The epidemiological features of AF are described in one of the largest population cohorts ever studied. METHODS: The prevalence and incidence of AF were studied in the Renfrew/Paisley population cohort of 15 406 men and women aged 45-64 years living in the west of Scotland. This cohort was initially screened between 1972 and 1976 and again between 1977 and 1979. Incident hospitalisations with AF in the 20 year period following initial screening were also studied. RESULTS: The population prevalence of AF in this cohort was 6.5 cases/1000 examinations. Prevalence was higher in men and older subjects. In those who were rescreened, the four year incidence of AF was 0.54 cases/1000 person years. Radiological cardiomegaly was the most powerful predictor of new AF (adjusted odds ratio 14.0). During 20 year follow up, 3.5% of this cohort was discharged from hospital with a diagnosis of AF; the rate of incident hospitalisation for AF was 1.9 cases/1000 person years. Radiological cardiomegaly (adjusted odds ratio 1.46) and systolic blood pressure (adjusted odds ratio 2.1 for >/= 169 mm Hg) were independent predictors of this outcome. CONCLUSIONS: Data from one of the largest epidemiological studies ever undertaken confirm that AF has a large population prevalence and incidence, even in middle aged people. More important, it was shown that the long term incidence of hospitalisation related to AF is high and that two simple clinical measurements are highly predictive of incident AF. These findings have important implications for the prevention of AF.

Age Distribution↗
PubMed2000

Induction of acrosomal exocytosis in chicken spermatozoa by inner perivitelline-derived N-linked glycans.

In birds, the ovum is surrounded by a glycoprotein coat known as the inner perivitelline layer (IPVL), which is analogous to the mammalian zona pellucida and, as such, is the site of initial sperm binding and induction of acrosomal exocytosis (the acrosome reaction). In this study, we demonstrate that oligosaccharides isolated from chicken-IPVL glycoproteins are capable of inducing the acrosome reaction in chicken spermatozoa. Preparations containing only O-linked glycans were unable to induce the acrosome reaction whereas N-linked oligosaccharides released from the IPVL by PNGaseF treatment could induce the acrosome reaction. Addition of galactose to terminal N-acetyglucosamine residues suppressed the acrosome reaction-inducing capacity of the oligosaccharide preparation; however, this capacity could be restored by co-incubation with beta-galactosidase. This evidence suggests that the acrosome reaction-inducing factor is probably an N-linked oligosaccharide with terminal N-acetyl-glucosamine residues.

Acetylglucosamine↗
PubMed2000

Regulation of STAT3 by direct binding to the Rac1 GTPase.

The signal transducers and activators of transcription (STAT) transcription factors become phosphorylated on tyrosine and translocate to the nucleus after stimulation of cells with growth factors or cytokines. We show that the Rac1 guanosine triphosphatase can bind to and regulate STAT3 activity. Dominant negative Rac1 inhibited STAT3 activation by growth factors, whereas activated Rac1 stimulated STAT3 phosphorylation on both tyrosine and serine residues. Moreover, activated Rac1 formed a complex with STAT3 in mammalian cells. Yeast two-hybrid analysis indicated that STAT3 binds directly to active but not inactive Rac1 and that the interaction occurs via the effector domain. Rac1 may serve as an alternate mechanism for targeting STAT3 to tyrosine kinase signaling complexes.

Amino Acid Substitution↗
PubMed2000

Evidence of improving prognosis in heart failure: trends in case fatality in 66 547 patients hospitalized between 1986 and 1995.

BACKGROUND: Contemporary survival in unselected patients with heart failure and the population impact of newer therapies have not been widely studied. Therefore, we have documented case-fatality rates (CFRs) over a recent 10-year period. METHODS AND RESULTS: In Scotland, all hospitalizations and deaths are captured on a single database. We have studied case fatality in all patients admitted with a principal diagnosis of heart failure from 1986 to 1995. A total of 66 547 patients (47% male) were studied. Median age was 72 years in men and 78 years in women. Crude CFRs at 30 days and at 1, 5, and 10 years were 19.9%, 44.5%, 76.5%, and 87.6%, respectively. Median survival was 1.47 years in men and 1.39 years in women (2.47 and 2. 36 years, respectively, in those surviving 30 days). Age had a powerful effect on survival, and sex, comorbidity, and deprivation had modest effects. One-year CF was 24.2% in those aged <55 years and 58.1% in those aged >84 years. After adjustment, 30-day CFRs fell between 1986 and 1995, by 26% (95% CI 15 to 35, P<0.0001) in men and 17% (95% CI 6 to 26, P<0.0001) in women. Longer term CFRs fell by 18% (95% CI 13 to 24, P<0.0001) in men and 15% (95% CI 10 to 20, P<0.0001) in women. Median survival increased from 1.23 to 1. 64 years. CONCLUSIONS: Heart failure CF is much higher in the general population than in clinical trials, especially in the elderly. Although survival has increased significantly over the last decade, there is still much room for improvement.

Aged↗
PubMed2000

The dominant negative Ras mutant, N17Ras, can inhibit signaling independently of blocking Ras activation.

Ras plays an important role in a variety of cellular functions, including growth, differentiation, and oncogenic transformation. For instance, Ras participates in the activation of Raf, which phosphorylates and activates mitogen-activated protein kinase kinase (MEK), which then phosphorylates and activates extracellular signal-regulated kinase (ERK), a mitogen-activated protein (MAP) kinase. Activation of MAP kinase appears to be essential for propagating a wide variety of extracellular signals from the plasma membrane to the nucleus. N17Ras, a GDP-bound dominant negative mutant, is used widely as an interfering mutant to assess Ras function in vivo. Surprisingly, we observed that expression of N17Ras inhibited the activity and phosphorylation of Elk-1, a physiological substrate of MAP kinases, in response to phorbol myristate acetate. The activity and phosphorylation of the MAP kinase hemagglutinin epitope (HA)-ERK1 were not affected by N17Ras in response to the same stimulus. Additionally, expression of N17Ras, but not L61S186Ras, a GTP-bound interfering mutant, inhibited MEK-induced Elk-1 phosphorylation, suggesting that inhibition of Elk-1 may be unique to GDP-bound Ras mutants. Finally, we observed that V12Ras-induced focus formation in NIH3T3 cells is inhibited by coexpression of GDP-bound Ras mutants, such as N17, A15, and N17N69. Therefore, N17Ras and V12 Ras may be codominant with respect to Elk-1 activation and cellular transformation. These results indicate that N17Ras appears to have at least two distinguishable functions: interference with endogenous Ras activation and inhibition of Elk-1 and transfomation. Furthermore, our data imply the possibility that GDP-bound Ras, like N17Ras, may have a direct role in signal transduction.

Cell Transformation, Neoplastic↗
PubMed2000

Changes in expression of the lysosomal membrane glycoprotein, LAMP-1 in interdigital regions during embryonic mouse limb development, in vivo and in vitro.

Syndactyly, a failure of the digits to separate into individual units, affects about 8 to 9 per 1000 newborns and results from an aberration of the normal development of the interdigital tissues. Limb digit separation is the result of programmed cell death (apoptosis). Lysosomes play a role in the process of cell self-destruction. Our experiment was designed to test the hypothesis that the intensity of interdigital lysosomes increases during the separation of digits in vivo and in vitro. The primary mouse monoclonal antibody, 1D4B, detects the presence of lysosomes by identifying the LAMP-1 glycoprotein on the lysosome cell membrane. In our experiment this antibody immunodetected interdigital lysosome proteins in serial sections of limbs from Swiss-Webster mouse embryos, gestational ages E12.5 through E15, key developmental stages for digit separation. Digit separation was associated with an increase in intensity of lysosomal protein staining. In E12.5 limbs, the presence of lysosomes was enriched in the distal aspect of the interdigital tissue. However, the number of lysosomes markedly increased in the E13 and E14 limbs, including the entire length and width of the interdigital tissue in the E14 limbs. This lysosomal protein presence in E14 limbs was significant compared to E12.5, E13, and E15 limbs. By day 12.5, the mouse embryo limb is committed to digit separation. Addition of retinoic acid to the culture medium of limbs earlier in development, such as E12, results in induction of the process of digit separation. Cultured E12 limbs that did not receive an addition of retinoic acid, did not show digit separation. We conclude that in the limb development process, the enrichment in interdigit LAMP-1 proteins, may indicate a relationship between lysosomes, apoptosis, and digit separation. We also conclude that retinoic acid has an important role in digit separation in vivo, as shown in limb development, and demonstrated through the addition of retinoic acid to media of cultured tissues.

Animals↗
PubMed2000

Improved RNA extraction and one-tube RT-PCR assay for simultaneous detection of control plant RNA plus several viruses in plant extracts.

A procedure was developed for simultaneous detection of plant RNA viruses and of plant RNA, as a control. RT-PCR amplification with primers designed for the detection of the plant mRNAs encoding malate dehydrogenase (MDH) and the large subunit of ribulose bisphosphate carboxylase oxygenase (RubiscoL) was used for the development of a plant extraction procedure that consistently yields extracts that can be amplified. The control amplification was used successfully on extracts from cane, leaf and/or bud tissues from grapevine, apple, raspberry, strawberry, peach, apricot, plum and wheat. Multiplex RT-PCR conditions were established for the simultaneous detection in grapevine extracts of either arabis mosaic virus, rupestris stem pitting associated virus and malate dehydrogenase mRNA, or grapevine virus A, grapevine virus B, grapevine leafroll associated virus-3, and RubiscoL mRNA.

Malate Dehydrogenase↗
PubMed2000

Investing in the future of cardiovascular nursing as a research based profession: an international perspective.

While we all face problems with promoting research even at a local level we must not lose sight of how much there is to gain from learning from each other. Together, on an international basis, we can make more progress in alleviating the suffering of our patients. The "head in the sand" approach (even on a nice warm beach in Australia or California) will be of little benefit to our patients or ourselves in the future. We must do more to take the good, but rare, examples of international collaboration in cardiovascular nursing and make them commonplace!

Australia↗
PubMed2000

Block Copolymer Nanotubes.

Rigid cylindrical micelles are made from polyisoprene-block-poly(2-cinnamoylethyl methacrylate)-block-poly(tert-butyl acrylate). The PI-PCEMA-PtBA polymer assembles to micelles with PI as the core, PCEMA as the shell, and PtBA as the corona. The cylindrical structure is fixed by photocrosslinking the PCEMA shell, and PCEMA-PtBA nanotubes are obtained by degrading the PI core with ozone (see scheme).

Journal Article↗