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Biomedical subjects

S Maguire

Publications and source records attributed to S Maguire.

At least 19 recordsLinked to original sources
PubMed2002

Variability of Nt-proANP and C-ANP.

BACKGROUND: Natriuretic peptides are frequently measured in patients with chronic cardiac failure (CCF). We set out to compare the variability of atrial natriuretic peptide (C-ANP) and its precursor N-terminal pro-ANP (Nt-proANP) to decide which would be more suitable for routine use. METHODS: Ten males with compensated CCF (age range 62-76 years) were studied, with matched controls. Blood was withdrawn every 2 min for 90 min from a forearm vein, and plasma C-ANP and Nt-proANP were measured by radioimmunoassay. RESULTS: Levels were elevated in the patient group [C-ANP: median 268 (range 171-423) vs. 40 (28-56) ng L-1, P < 0.0002 Mann-Whitney U-test; Nt-proANP: 1955 (562-4451) vs. 621 (409-961) pmol L-1, P < 0.003]. A similar number of 'peaks' was observed in both groups with both peptides, about one every 10 min, and their relative height was similar in both groups. Variability was greater for C-ANP than for Nt-proANP in both patients [coefficient of variation of means 51 (range 36-70) vs. 3.6 (2.1-6.2)%, P < 0.01; sign test] and controls [65 (49-83) vs. 8.9 (4.7-13.5)%, P < 0.01]. CONCLUSION: Nt-proANP is less variable than C-ANP and hence more suited for diagnostic or prognostic use.

Aged↗
PubMed2001

Adult human olfactory stem cells.

The location of stem cells within the adult CNS makes them impractical for surgical removal and autologous transplantation. Their limited availability and histocompatibility issues further restrict their use. In contrast, olfactory neuroepithelium (ONe) located in the nasal passageways has a continuous regenerative capability and can be biopsied readily. To investigate the potential of human ONe to provide viable populations of pluripotent cells, ONe was harvested from cadavers 6-18 h postmortem, dissociated, plated and fed every 3-4 days. Heterogeneous populations of neurons, glia, and epithelia were identified with lineage-specific markers. After several weeks, 5-10% of the cultures produced a population of rapidly dividing cells, which in turn, produced neurospheres containing at least two subpopulations based on neuronal and glial specific antigens. Most contained one or more neuronal markers; a few were positive for A2B5 and/or GFAP. To determine if growth modulators would affect the neurosphere forming cells, they were exposed to dibutyryl-cAMP. The nucleotide reduced cell division and increased process formation. Although the cells had been passaged more than 70 times, their viability remained constant as shown by the MTT viability index. Donor age or sex were not limiting factors, because neurospheres have been established from cadavers of both sexes from 50 to 95 years old at time of death. The ex vivo expansion of these cells will provide a patient-specific population of cells for immunological, genetic and pharmacological evaluation. Our long-term goal is to determine the utility of these cells to facilitate CNS repair.

Aged↗
PubMed2001

Rrb1p, a yeast nuclear WD-repeat protein involved in the regulation of ribosome biosynthesis.

Ribosome biogenesis is regulated by environmental cues that coordinately modulate the synthesis of ribosomal components and their assembly into functional subunits. We have identified an essential yeast WD-repeat-containing protein, termed Rrb1p, that has a role in both the assembly of the 60S ribosomal subunits and the transcriptional regulation of ribosomal protein (RP) genes. Rrb1p is located in the nucleus and is concentrated in the nucleolus. Its presence is required to maintain normal cellular levels of 60S subunits, 80S ribosomes, and polyribosomes. The function of Rrb1p in ribosome biogenesis appears to be linked to its association with the ribosomal protein rpL3. Immunoprecipitation of Rrb1p from nuclear extracts revealed that it physically interacts with rpL3. Moreover, the overproduction of Rrb1p led to increases in cellular levels of free rpL3 that accumulated in the nucleus together with Rrb1p. The concentration of these proteins within the nucleus was dependent on ongoing protein translation. We also showed that overexpression of RRB1 led to an increase in the expression of RPL3 while all other examined RP genes were unaffected. In contrast, depletion of RRB1 caused an increase in the expression of all RP genes examined except RPL3. These results suggest that Rrb1p regulates RPL3 expression and uncouples it from the coordinated expression of other RP genes.

Alleles↗
PubMed2000

Pyogenic liver abscess.

BACKGROUND: A current assessment of liver abscesses should allow for better understanding of the pathogenesis of the disease and improve the effectiveness of diagnosis and treatment. Amebic liver abscess occurs more commonly than pyogenic liver abscess on a worldwide basis. However, in the United States, pyogenic liver abscess predominates. The purpose of our study was to evaluate the etiology, management, morbidity, and mortality of all patients admitted to our medical center with diagnoses of pyogenic liver abscess between 1983 and 1996. METHODS: A retrospective chart review was performed on all patients admitted to our medical center, Louisiana State University Medical Center, Shreveport, with diagnoses of pyogenic liver abscess. RESULTS: Twenty patients were admitted with diagnoses of pyogenic liver abscess. The subjects were 65% (13/20) male and 65% (13/20) African-American and had an average age of 52 years. The most common presenting symptoms were fever and pain. The most common physical finding was right upper-quadrant tenderness. The most common etiologies of pyogenic liver abscesses were cryptogenic, trauma, and biliary, while portal vein was the source for only 10% of the cases. The right lobe of the liver was involved in 95% of the cases, and 70% of these liver abscesses were solitary. Computed tomography (CT)-and ultrasound-guided percutaneous drainage were performed in 85% (17/20) of patients with liver abscesses. One patient was treated by open drainage, three patients were treated with antibiotics alone, and three patients did not respond to aspiration and catheter placement, which subsequently required open drainage. The culture results were as follows: 50% were gram-negative organisms, 25% were gram-positive organisms, 10% were anaerobic organisms, and 15% of the abscess were sterile. Sixty percent of the positive abscess cultures were polymicrobial. CONCLUSIONS: CT scan- and ultrasound-guided percutaneous drainage of pyogenic liver abscesses were safe and effective methods of treatment. The right lobe of the liver was involved in 95% of cases. Although no one species predominated, gram-negative bacteria were the most common organism cultured, and 60% of the abscesses were polymicrobial. There was no in-house mortality in this review.

Adult↗
PubMed2000

Vasoconstriction to endogenous endothelin-1 is impaired in patients with type II diabetes mellitus.

Endothelin-1 has potent vasoconstrictor and vasopressor actions contributing to basal vascular tone and maintenance of blood pressure acting predominantly through endothelin-A receptors. Endothelin antagonists may be of value in the treatment of hypertension and heart failure. However, the role of endothelin-1 in the regulation of vascular tone and the potential benefits of endothelin antagonists in non-insulin-dependent diabetes mellitus (Type II diabetes) are less clear. Vasoconstriction to exogenous endothelin-1 is impaired in Type II diabetes. The purpose of this study was to determine whether vasoconstriction to endogenous endothelin-1 acting through the endothelin-A receptor is impaired in Type II diabetes. In ten patients with Type II diabetes and nine controls the endothelin-A receptor antagonist BQ123 was infused intra-arterially at 100 nmol/min for 60 min followed by normal saline for 30 min. Forearm blood flow was measured using venous occlusion plethysmography. Control subjects showed gradual onset of vasodilation in response to BQ123 (P < 0.001). Diabetic subjects, however, showed no significant response (P > 0.05). There was a significant difference between the diabetic and control groups (P < 0.05). Blockade of the endothelin-A receptor is associated with impaired vasodilation in Type II diabetes indicating vasoconstriction to endogenous endothelin-1 mediated by the endothelin-A receptor is impaired.

Adult↗
PubMed1999

Combining serial analysis of gene expression and array technologies to identify genes differentially expressed in breast cancer.

Several methods have been used recently to determine gene expression profiles of cell populations. Here we demonstrate the strength of combining two approaches, serial analysis of gene expression (SAGE) and DNA arrays, to help elucidate pathways in breast cancer progression by finding genes consistently expressed at different levels in primary breast cancers, metastatic breast cancers, and normal mammary epithelial cells. SAGE profiles of 21PT and 21MT, two well-characterized breast tumor cell lines, were compared with SAGE profiles of normal breast epithelial cells to identify differentially expressed genes. A subset of these candidates was then placed on an array and screened with clinical breast tumor samples to find genes and expressed sequence tags that are consistently expressed at different levels in diseased and normal tissues. In addition to finding the predicted overexpression of known breast cancer markers HER-2/neu and MUC-1, the powerful coupling of SAGE and DNA arrays resulted in the identification of genes and potential pathways not implicated previously in breast cancer. Moreover, these techniques also generated information about the differences and similarities of expression profiles in primary and metastatic breast tumors. Thus, combining SAGE and custom array technology allowed for the rapid identification and validation of the clinical relevance of many genes potentially involved in breast cancer progression. These differentially expressed genes may be useful as tumor markers and prognostic indicators and may be suitable targets for various forms of therapeutic intervention.

Biomarkers, Tumor↗
PubMed1999

Primary squamous cell carcinoma of the parotid gland: the importance of correct histological diagnosis.

BACKGROUND: Primary squamous cell carcinoma of the parotid is an uncommon, aggressive malignancy with a poor prognosis. The diagnosis is made after excluding metastasis from other sites in the head and neck or other primary malignancies of the parotid. METHODS: Tumor registry data from 1974 to 1994 were reviewed at three University of Louisville-affiliated hospitals. Of 370 parotid tumors, 40 (11%) were initially classified as squamous cell carcinoma of the parotid. Chart review and histological specimen re-examination were conducted to confirm diagnosis. RESULTS: Only 8 (2%) of the 370 cases, were considered true primary squamous cell carcinoma of the parotid. Patients with metastases to the parotid from primary sites within the upper aerodigestive tract or skin of the head and neck region and high-grade mucoepidermoid carcinoma of the parotid were excluded. Facial nerve dysfunction was a presenting complaint in three patients. Two patients presented with American Joint Committee on Cancer (AJC) clinical stage III disease and six with AJC stage IV disease. All patients were treated with total parotidectomy and radiotherapy. One patient (12%) is alive and free of disease. Median survival was 13 months (range, 11 months-7 years). CONCLUSIONS: Primary squamous cell carcinoma of the parotid is uncommon, occurring in 2% of parotid neoplasms at our institution. This is an aggressive malignancy, usually presenting in advanced stage and with facial nerve involvement or cervical metastases. Prognosis is poor even with radical surgery and adjunctive radiotherapy. Careful clinical and histological review is necessary to differentiate primary squamous cancer of the parotid from metastases or other primary parotid malignancy.

Aged↗
PubMed1999

Forearm reactive hyperaemia is not mediated by nitric oxide in healthy volunteers.

AIMS: To determine the role of nitric oxide (NO) in forearm reactive hyperaemia in healthy human subjects. METHODS: Ten healthy subjects aged 19-34 years underwent brachial artery cannulation. Forearm circulatory arrest was achieved by means of an upper arm cuff inflated to 200 mmHg for 5 min. The blood flow responses during reactive hyperaemia were measured using venous occlusion plethysmography following a 10 min intra-arterial infusion of 8 micromol min-1 N-monomethyl L-arginine (L-NMMA) and following matching placebo administered in random order. Results were analysed by repeated measures anova and t-tests. RESULTS: L-NMMA resulted in a significant reduction of basal forearm blood flow indicating inhibition of basal NO release (P=0.005). There was no significant difference between the blood flow responses during reactive hyperaemia following L-NMMA and placebo (P=0.97). CONCLUSIONS: Nitric oxide production does not make a significant contribution to the vasodilatation associated with reactive hyperaemia in the human forearm.

Adult↗
PubMed1998

Body composition and energy expenditure of patients with chronic cardiac failure.

BACKGROUND: Patients with acute cardiac failure have excess body water, and it is commonly assumed that this is also so in patients with stable chronic cardiac failure (CCF). METHODS: To investigate this, we measured total body water (TBW) using stable isotope dilution and single-frequency bioelectrical impedance (BIA), and also extracellular volume (ECV) using bromide dilution in 12 patients with CCF and eight matched control subjects. RESULTS: TBW [kg(-1) bodyweight] was similar in the two groups [median 18O dilution 53.2% (range 46.5-57.1%) in patients vs. 54.8% (47.9-62.7) in control subjects; BIA 56.6% (42.7-73.1) vs. 58.0% (52.0-68.6)]. ECV was also similar in the two groups [0.25 Lkg(-1) (0.20-0.29) vs. 0.25 (0.19-0.35)]. There was a strong correlation between stable isotope and BIA measurements of TBW for all subjects (r = 0.76), but BIA overestimated TBW by a mean difference of 2.4 kg (limits of agreement of -4.1 kg to +8.9 kg). Body fat content was similar in the two groups, whether measured by skinfold anthropometry, whole-body densitometry or by 18O dilution. Resting energy expenditure (REE), calculated from indirect calorimetry, and total energy expenditure (TEE), calculated from the ratio of 2H to 18O elimination rate after drinking doubly labelled water, were also similar in the two groups. CONCLUSION: It is concluded that the patients with stable CCF in this study had normal ECV and TBW, and so excess body water did not account for their persistent symptoms.

Aged↗
PubMed1997

Forearm endothelium-dependent vascular responses and the potassium-ATP channel.

AIMS: Vasodilation to acetylcholine is mediated at least in part by endothelium-derived hyperpolarising factor (EDHF) which causes membrane hyperpolarisation by activating potassium channels. It is however uncertain which potassium channel mediates this effect. The aim of this study was to determine the role of the potassium-ATP (K(+)-ATP) channel in mediating endothelium-dependent vascular responses to acetylcholine. METHODS: In 10 healthy volunteers acetylcholine, an endothelium-dependent vasodilator, and sodium nitroprusside as a control assessing endothelium-independent vasodilatation were infused into the non-dominant brachial artery. Forearm blood flow (FBF) in response to each dose was measured by strain-gauge venous occlusion plethysmography. The K(+)-ATP channel blocker glipizide (2.5 mg) was then administered orally. After 45 min the infusions with FBF measurements were repeated. RESULTS: Acetylcholine (P < 0.01) and sodium nitroprusside (P < 0.01) both caused an increase in FBF. There was no significant difference in vascular responses to acetylcholine (P > 0.05) or sodium nitroprusside (P > 0.05) following K(+)-ATP channel blockade. CONCLUSIONS: The K(+)-ATP channel does not modulate forearm arteriolar endothelium-dependent responses in healthy volunteers and therefore does not play a role in membrane hyperpolarisation.

Acetylcholine↗
PubMed1996

Cytokine profile in chronic cardiac failure.

Elevated tumour necrosis factor alpha (TNF-alpha) has been demonstrated in chronic cardiac failure (CCF) and may relate to severity of CCF and development of cachexia. We measured TNF receptor p55 in addition to TNF-alpha in an attempt to improve the detection rate of TNF-alpha activation, and simultaneously measured interleukin 6 (IL-6), interleukin 8 (IL-8) and C-reactive protein. Thirty-four patients with CCF and 24 control subjects were studied. Only TNF receptor p55 [6.95 (0.77-42.3) vs. 5.52 (1.50-13.36) ng mL-1 (median (range)] and IL-6 [0.335 (0-9.79) vs. 0(0-14.71) pg mL-1) were significantly elevated in patients compared with control subjects (both P < 0.05). All inflammatory markers were more frequently elevated in patients, but none correlated with any of the clinical parameters studied. Reasons for inflammatory marker elevation in CCF are uncertain, but future studies should measure the p55 TNF receptor and IL-6 in addition to TNF-alpha, to improve detection of cytokine activity.

Aged↗
PubMed1996

The yeast nucleoporin Nup188p interacts genetically and physically with the core structures of the nuclear pore complex.

We have isolated a major protein constituent from a highly enriched fraction of yeast nuclear pore complexes (NPCs). The gene encoding this protein, Nup188p, was cloned, sequenced, and found to be nonessential upon deletion. Nup188p cofractionates with yeast NPCs and gives an immunofluorescent staining pattern typical of nucleoporins. Using immunoelectron microscopy, Nup188p was shown to localize to both the cytoplasmic and nucleoplasmic faces of the NPC core. There, Nup188p interacts with an integral protein of the pore membrane domain, Pom152p, and another abundant nucleoporin, Nic96p. The effects of various mutations in the NUP188 gene on the structure of the nuclear envelope and the function of the NPC were examined. While null mutants of NUP188 appear normal, other mutants allelic to NUP188 exhibit a dominant effect leading to the formation of NPC-associated nuclear envelope herniations and growth inhibition at 37 degrees C. In addition, depletion of the interacting protein Pom152p in cells lacking Nup188p resulted in severe deformations of the nuclear envelope. We suggest that Nup188p is one of a group of proteins that form the octagonal core structure of the NPC and thus functions in the structural organization of the NPC and nuclear envelope.

Amino Acid Sequence↗
PubMed1995

Information management and technology in England's large acute NHS hospitals. National strategy versus local reality.

Discusses the NHS Executive's information management and technology (IM&T) strategy and its relationship to the 1991 reforms. Examines the recommendation for large acute hospitals to adopt integrated hospital information support systems (HISS). Reports that a recent census of these hospitals, undertaken by the authors, suggests that the implementation of the strategy's recommendations has been slow at the local level. Attempts to diagnose the factors that are impeding implementation, using the evidence provided by the census. Identifies four main problem areas: the lack of success of past IM&T initiatives undermines confidence in the current strategy; the strategy is poorly aligned with other policy initiatives; the legacy of discrete, proprietary information systems within hospitals makes the creation of an integrative information environment difficult to accomplish without massive investment in new systems; and there are implicit contradictions between the following: the absence of a comprehensive post-implementation evaluation of the economic, technological and cultural feasibility of HISS at any of the three HISS pilot sites; the strategy's advocacy of HISS as the way forward for large acute hospitals; the requirement for a comprehensive business case to support any substantial investment in IM&T. Concludes that a massive rethink of policy is required, with a much greater emphasis on research, development and independent evaluation.

Confidentiality↗