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Biomedical subjects

M A Smith

Publications and source records attributed to M A Smith.

At least 127 records · Page 7Linked to original sources
PubMed2001

Measuring the physician perspective on quality of care in health plans.

Physicians provide one source of information about the quality of care in health plans, but concerns exist that physicians cannot distinguish quality from financial considerations or other underlying attitudes. We examined whether physicians can (a) distinguish different domains of health plan quality and (b) distinguish health plan quality from their underlying attitudes. We analyzed data on 419 generalist physicians from four health plans. Three scales assessed physicians' perceptions of facilitators and barriers to high-quality care in the plans and the clinical capabilities of plan physicians. Structural equation modeling indicated that physicians could distinguish domains of health plan quality. Physicians could also distinguish plan quality from their attitudes toward the plan, but plan quality was more highly correlated with general managed care attitudes than expected. These data suggest that physicians can provide information about health plan quality, but it will be important to validate these measures against patient outcomes.

Attitude of Health Personnel↗
PubMed2001

Effect of the herbicide 4-CPA on human erythrocyte antioxidant enzymes in vitro.

To investigate the possible role of oxygen free radicals and oxidant stress in the toxic effects of phenoxyherbicides, we studied the in vitro effect of 4-chlorophenoxyacetic acid (4-CPA) on various human erythrocyte antioxidant enzymes, namely glucose-6-phosphate dehydrogenase, catalase, selenium-dependent glutathione peroxidase, glutathione reductase and Cu/Zn-superoxide dismutase. 4-CPA added in a dose of 1 ppm to human erythrocytes for 1 h caused a significant reduction in glucose-6-phosphate dehydrogenase (P <0.001) and catalase (P <0.001) activities, but did not significantly affect the activities of other enzymes. Such selective inactivation of specific erythrocyte antioxidant enzymes may play a role in the toxic effects of phenoxyherbicides.

2,4-Dichlorophenoxyacetic Acid↗
PubMed2001

Chemistry and biochemistry of oxidative stress in neurodegenerative disease.

The age-related neurodegenerative diseases exemplified by Alzheimer&hyp;s disease (AD), Lewy body diseases such as Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington&hyp;s disease are characterized by the deposition of abnormal forms of specific proteins in the brain. Although several factors appear to underlie the pathological depositions, the cause of neuronal death in each disease appears to be multifactorial. In this regard, evidence in each case for a role of oxidative stress is provided by the finding that the pathological deposits are immunoreactive to antibodies recognizing protein side-chains modified either directly by reactive oxygen or nitrogen species, or by products of lipid peroxidation or glycoxidation. Although the source(s) of increased oxidative damage are not entirely clear, the findings of increased localization of redox-active transition metals in the brain regions most affected is consistent with their contribution to oxidative stress. It is tempting to speculate that free radical oxygen chemistry plays a pathogenetic role in all these neurodegenerative conditions, though it is as yet undetermined what types of oxidative damage occur early in pathogenesis, and what types are secondary manifestations of dying neurons. Delineation of the profile of oxidative damage in each disease will provide clues to how the specific neuronal populations are differentially affected by the individual disease conditions.

Alzheimer Disease↗
PubMed2001

Pharmacologic characterization of BMS-191095, a mitochondrial K(ATP) opener with no peripheral vasodilator or cardiac action potential shortening activity.

Previous work described ATP-sensitive K(+) channel (K(ATP)) openers (e.g., BMS-180448), which retain the cardioprotective activity of agents such as cromakalim while being significantly less potent as vasodilators. In this study, we describe the pharmacologic profile of BMS-191095, which is devoid of peripheral vasodilating activity while retaining glyburide-reversible cardioprotective activity. In isolated rat hearts subjected to 25 min of global ischemia and 30 min of reperfusion, BMS-191095 increased the time to onset of ischemic contracture with an EC(25) of 1.5 microM, which is comparable to 4.7 microM and 3.0 microM for cromakalim and BMS-180448, respectively. Comparisons of cardioprotective and vasorelaxant potencies in vitro and in vivo showed BMS-191095 to be significantly more selective for cardioprotection with virtually no effect on peripheral smooth muscle, whereas cromakalim showed little selectivity. In addition to increasing the time to the onset of contracture, BMS-191095 improved postischemic recovery of function and reduced lactate dehydrogenase release in the isolated rat hearts. The cardioprotective effects of BMS-191095 were abolished by glyburide and sodium 5-hydroxydecanoate (5-HD). BMS-191095 did not shorten action potential duration in normal or hypoxic myocardium within its cardioprotective concentration range nor did it activate sarcolemmal K(ATP) current (< or =30 microM). BMS-191095 opened cardiac mitochondrial K(ATP) with a K(1/2) of 83 nM, and this was abolished by glyburide and 5-HD. These results show that the cardioprotective effects of BMS-191095 are dissociated from peripheral vasodilator and cardiac sarcolemmal K(ATP) activation. Agents like BMS-191095 may owe their cardioprotective selectivity to selective mitochondrial K(ATP) activation.

Action Potentials↗
PubMed2001

C-kit mutation screening in patients with acute myeloid leukaemia: adaptation of a Giemsa-stained bone-marrow smear DNA extraction technique.

The scarcity of viable tissue samples for leukaemia research is widely recognised and currently restrictive. Archival bone-marrow smears present a valuable resource that can be exploited easily for mutational analysis. Here, a modified technique to extract DNA is described, and used subsequently for mutation/polymorphism screening of the stem-cell factor receptor proto-oncogene c-kit in 23 patients with acute myeloid leukaemia (AML). The selected method was straightforward and used bone-marrow material scraped from periodic acid-Schiff, sudan black B and May-Grünwald/Giemsa-stained preparations, and treated initially with proteinase K prepared in digestion buffer to digest all proteinaceous matter. Following incubation, saturated sodium chloride was added and DNA extracted from the supernatant by phenol/chloroform/isoamyl alcohol treatment. Retrieved DNA was precipitated with ethanol at -20 degrees C overnight, washed with 95% ethanol, air-dried, resuspended using purite water and stored at -20 degrees C prior to use in mutational analysis. The extraction method described was compared with a commercial reagent for combined DNA, RNA and protein isolation using cryopreserved cells from 20 patients with AML. The quality of extracted DNA isolated by the two methods was comparable by polymerase chain reaction (PCR) and single-strand conformation polymorphism (SSCP) techniques. Bone-marrow biopsies are performed regularly on each AML patient to monitor the disease; therefore, an extraction method using this resource could liberate a valuable source of DNA for study (e.g. molecular investigations, including mutation/polymorphism screening etc.). This would allow fresh and programme-frozen cells to be reserved for those investigations requiring intact, viable cells. The use of archived bone-marrow smears would permit vast increase in the scope for retrospective testing and large-scale analyses.

Acute Disease↗
PubMed2001

The cost-effectiveness of a patient-sitter program in an acute care hospital: a test of the impact of sitters on the incidence of falls and patient satisfaction.

This article analyzes the costs and benefits of a patient-sitter program in relation to patient falls and patient satisfaction. During these days of intense budgetary scrutiny, it is necessary to integrate methods of cost/benefit analysis into our loss prevention management programs, whether physical loss or loss patient base due to dissatisfied patients. This article presents the research we have conducted to analyze costs and benefits of our patient-sitter program in relation to patient falls and patient satisfaction.

Accident Prevention↗
PubMed2001

A condensing enzyme from the seeds of Lesquerella fendleri that specifically elongates hydroxy fatty acids.

Lesquerella fendleri seed oil contains up to 60% hydroxy fatty acids, nearly all of which is the 20-carbon hydroxy fatty acid lesquerolic acid (D-14-hydroxyeicos-cis-11-enoic acid). Previous work suggested that lesquerolic acid in L. fendleri was formed by the elongation of the 18-carbon hydroxy fatty acid, ricinoleic acid. To identify a gene encoding the enzyme involved in hydroxy fatty acid elongation, an L. fendleri genomic DNA library was screened using the coding region of the Arabidopsis Fatty Acid Elongation1 gene as a probe. A gene, LfKCS3, with a high sequence similarity to known very long-chain fatty acid condensing enzymes, was isolated. LfKCS3 has a 2,062-bp open reading frame interrupted by two introns, which encodes a polypeptide of 496 amino acids. LfKCS3 transcripts accumulated only in the embryos of L. fendleri and first appeared in the early stages of development. Fusion of the LfKCS3 promoter to the uidA reporter gene and expression in transgenic Arabidopsis resulted in a high level of beta-glucuronidase activity exclusively in developing embryos. Seeds of Arabidopsis plants transformed with LfKCS3 showed no change in their very long-chain fatty acid content. However, when these Arabidopsis plants were crossed with the transgenic plants expressing the castor oleate 12-hydroxylase, significant amounts of 20-carbon hydroxy fatty acids accumulated in the seed, indicating that the LfKCS3 condensing enzyme specifically catalyzes elongation of 18-carbon hydroxy fatty acids.

Acetyltransferases↗
PubMed2001

The measurement of total body potassium in patients on peritoneal dialysis.

OBJECTIVES: To assess the validity of measuring total body potassium (TBK) to estimate fat-free mass (FFM) and body cell mass (BCM) in patients on peritoneal dialysis (PD). METHODS: We studied 29 patients on PD (14 men, 15 women) and 30 controls (15 men, 15 women). We calculated TBK by using a whole-body counter to measure 1.46 MeV gamma-ray emissions from naturally occurring 40K. We measured total body water (TBW) by deuterium oxide dilution, and extracellular water (ECW) from bromide dilution. These measurements allowed us to estimate intracellular water (ICW), fat-free mass dilution (FFM(Dilution)), and body cell mass dilution (BCM(Dilution)). RESULTS: The FFM(TBK) in male PD patients (55.7 +/- 7.0 kg) did not differ from that in male controls (57.0 +/- 10.9 kg). The FFM(TBK) in female PD patients (38.4 +/- 6.8 kg) was less than that in female controls (44.7 +/- 4.5, p < 0.01). The FFM(Dilution) did not differ from the FFM(TBK). Correlation of FFM(TBK) and FFM(Dilution) was r = 0.90, p < 0.0001 for all subjects; r = 0.90, p < 0.0001 for PD patients; and r = 0.90, p < 0.0001 for controls. Bland-Altman comparison of FFM(Dilution) with FFM(TBK) in individuals showed bias 0.6 kg, range -8.5 kg to 9.7 kg for the whole group; bias 1.4 kg, range -7.9 kg to 10.7 kg for PD patients; and bias -0.2 kg, range -9.0 kg to 8.6 kg for controls. The BCM(TBK) in male PD patients (30.1 +/- 4.5 kg) did not differ from that in male controls (31.9 +/- 6.2 kg). The BCM(TBK) in female PD patients (19.0 +/- 4.4 kg) was less than that in female controls (23.1 +/- 2.9 kg, p < 0.01). The BCM(Dilution) results did not differ from those for the BCM(TBK). Correlation of BCM(TBK) and BCM(Dilution) was r = 0.90, p < 0.0001 for all subjects; r = 0.87, p < 0.0001 for PD patients; and r = 0.93, p < 0.0001 for controls. Bland-Altman comparison of BCM(Dilution) with BCM(TBK) in individuals showed bias 0.1 kg, range -5.9 kg to 6.1 kg for the whole group; bias 0.0 kg, range -6.9 kg to 6.9 kg for PD patients; and bias 0.1 kg, range -5.0 kg to 5.2 kg for controls. The [K+]ICW did not differ between PD patients and controls (148.0 +/- 25.1 mmol/L vs 148.1 +/- 14.3 mmol/L, p = nonsignificant). CONCLUSIONS: Total body potassium is a valid, noninvasive technique for measuring FFM and BCM in PD patients. In our PD patient group, depletion of FFM and BCM as compared with controls was identified in the women but not in the men.

Body Composition↗
PubMed2000

Phosphorylated, but not native, tau protein assembles following reaction with the lipid peroxidation product, 4-hydroxy-2-nonenal.

A correlation between hyperphosphorylation of tau protein and its aberrant assembly into paired helical filaments has lead to suggestions that phosphorylation controls assembly, but lacked a mechanistic basic. In this work, we have found that phosphorylated, but not native, tau protein is able to form polymers after the reaction with 4-hydroxy-2-nonenal, a highly toxic product of lipid peroxidation. Phosphorylation of tau by both proline or non-proline directed kinases, was able to assemble it into polymers.

Aldehydes↗
PubMed2000

The rational clinical examination. Does this patient have strep throat?

CONTEXT: Sore throat is a common complaint, and identifying patients with group A beta-hemolytic streptococcal pharyngitis (strep throat) is an important task for clinicians. Previous reviews have not systematically reviewed and synthesized the evidence. OBJECTIVE: To review the precision and accuracy of the clinical examination in diagnosing strep throat. DATA SOURCE: MEDLINE search for articles about diagnosis of strep throat using history-taking and physical examination. STUDY SELECTION: Large blinded, prospective studies (having > or =300 patients with sore throat) reporting history and physical examination data and using throat culture as the reference standard were included. Of 917 articles identified by the search, 9 met all inclusion criteria. DATA EXTRACTION: Pairs of authors independently reviewed each article and used consensus to resolve discrepancies. DATA SYNTHESIS: The most useful findings for evaluating the likelihood of strep throat are presence of tonsillar exudate, pharyngeal exudate, or exposure to strep throat infection in the previous 2 weeks (positive likelihood ratios, 3.4, 2.1, and 1.9, respectively) and the absence of tender anterior cervical nodes, tonsillar enlargement, or exudate (negative likelihood ratios, 0.60, 0.63, and 0.74, respectively). No individual element of history-taking or physical examination is accurate enough by itself to rule in or rule out strep throat. Three validated clinical prediction rules are described for adult and pediatric populations. CONCLUSIONS: While no single element of history-taking or physical examination is sufficiently accurate to exclude or diagnose strep throat, a well-validated clinical prediction rule can be useful and can help physicians make more informed use of rapid antigen tests and throat cultures.

Adult↗
PubMed2000

Quantitative evaluation of the rRNA in Alzheimer's disease.

The ribosomal RNA (rRNA) genes are located in nucleolus during active transcription and are transcribed by RNA polymerase I. This group of genes is involved in transcription and translation processes which can modulate gene expression. The association between rRNA levels and aging has been reported. In the present study, we investigated the ratio of mature rRNA 28S and 18S in peripheral blood of 15 Alzheimer's disease (AD) patients, 15 elderly healthy controls and 15 healthy young controls. Our results showed a statistically significant decrease of the mature rRNA 28S/18S ratio in AD patients when compared with the elderly and young control groups. Thus we can suggest that there is a possible change in the transcriptional or maturation process or a preferential degradation of the 28S subunit in AD.

Adult↗
PubMed2000

Identification of ubiquilin, a novel presenilin interactor that increases presenilin protein accumulation.

Mutations in the highly homologous presenilin genes encoding presenilin-1 and presenilin-2 (PS1 and PS2) are linked to early-onset Alzheimer's disease (AD). However, apart from a role in early development, neither the normal function of the presenilins nor the mechanisms by which mutant proteins cause AD are well understood. We describe here the properties of a novel human interactor of the presenilins named ubiquilin. Yeast two-hybrid (Y2H) interaction, glutathione S-transferase pull-down experiments, and colocalization of the proteins expressed in vivo, together with coimmunoprecipitation and cell fractionation studies, provide compelling evidence that ubiquilin interacts with both PS1 and PS2. Ubiquilin is noteworthy since it contains multiple ubiquitin-related domains typically thought to be involved in targeting proteins for degradation. However, we show that ubiquilin promotes presenilin protein accumulation. Pulse-labeling experiments indicate that ubiquilin facilitates increased presenilin synthesis without substantially changing presenilin protein half-life. Immunohistochemistry of human brain tissue with ubiquilin-specific antibodies revealed prominent staining of neurons. Moreover, the anti-ubiquilin antibodies robustly stained neurofibrillary tangles and Lewy bodies in AD and Parkinson's disease affected brains, respectively. Our results indicate that ubiquilin may be an important modulator of presenilin protein accumulation and that ubiquilin protein is associated with neuropathological neurofibrillary tangles and Lewy body inclusions in diseased brain.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Clotrimazole inhibits lung fibroblast proliferation in vitro: implications for use in the prevention and treatment of obliterative bronchiolitis after lung transplantation.

BACKGROUND: Immunosuppressive therapy has limited activity against the mesenchymal cell proliferation of obliterative bronchiolitis. Clotrimazole (CLT) has been shown to inhibit proliferation in normal and cancer cell lines. Here we investigate whether CLT inhibits the proliferation of lung mesenchymal cells. METHODS: Proliferation of human lung fibroblasts (MRC-5) in the presence of CLT was determined by [3H]thymidine incorporation. Messenger ribonucleic acid (mRNA) expression of platelet-derived growth factor (PDGF)-B and transforming growth factor (TGF)-beta after treatment with CLT was measured by reverse transcriptase-polymerase chain reaction. RESULTS: Treatment of MRC-5 cells with CLT resulted in a significant reduction in proliferation as assessed by DNA incorporation and cell counts compared with dimethylsulfoxide alone. There was no cytotoxic effect associated with CLT treatment. Reverse transcriptase-polymerase chain reaction demonstrated a marked decrease in PDGF-B and TGF-beta mRNA levels in cells treated with CLT compared with those treated with dimethylsulfoxide. CONCLUSION: CLT inhibits proliferation of human lung fibroblasts. This inhibitory effect is associated with decreased levels of PDGF-B and TGF-beta mRNA expression and may have value in the prevention and treatment of obliterative bronchiolitis.

Bronchiolitis Obliterans↗
PubMed2000

Oxidative stress in Alzheimer's disease.

Oxidative balance is emerging as an important issue in understanding the pathogenesis of Alzheimer's disease. Examination of Alzheimer's disease brain has demonstrated a great deal of oxidative damage, associated with both hallmark pathologies (senile plaques and neurofibrillary tangles) as well as in normal appearing pyramidal neurons. While this suggests that oxidative stress is a proximal event in Alzheimer's disease pathogenesis, the mechanisms by which redox balance is altered in the disease remains elusive. Determining which of the proposed sources of free radicals, which include mitochondrial dysfunction, amyloid-beta-mediated processes, transition metal accumulation and genetic factors like apolipoprotein E and presenilins, is responsible for redox imbalance will lead to a better understanding of Alzheimer's disease pathogenesis and novel therapeutic approaches.

Alzheimer Disease↗
PubMed2000

Cyclin' toward dementia: cell cycle abnormalities and abortive oncogenesis in Alzheimer disease.

Recent evidence has associated the aberrant, proximal re-expression of various cell cycle control elements with neuronal vulnerability in Alzheimer disease, a chronic neurodegeneration. Such ectopic localization of various cyclins, cyclin-dependent kinases, and cyclin inhibitors in neurons can be seen as an attempt to re-enter the cell cycle. Given that primary neurons are terminally differentiated, any attempted re-entry into the cell division cycle in this postmitotic environment will be dysregulated. Since successful dysregulation of the cell cycle is also the hallmark of a neoplasm, early cell-cycle pathophysiology in Alzheimer disease may recruit oncogenic signal transduction mechanisms and, hence, can be viewed as an abortive neoplastic transformation.

Alzheimer Disease↗
PubMed2000

Evidence that the beta-amyloid plaques of Alzheimer's disease represent the redox-silencing and entombment of abeta by zinc.

Abeta binds Zn(2+), Cu(2+), and Fe(3+) in vitro, and these metals are markedly elevated in the neocortex and especially enriched in amyloid plaque deposits of individuals with Alzheimer's disease (AD). Zn(2+) precipitates Abeta in vitro, and Cu(2+) interaction with Abeta promotes its neurotoxicity, correlating with metal reduction and the cell-free generation of H(2)O(2) (Abeta1-42 > Abeta1-40 > ratAbeta1-40). Because Zn(2+) is redox-inert, we studied the possibility that it may play an inhibitory role in H(2)O(2)-mediated Abeta toxicity. In competition to the cytotoxic potentiation caused by coincubation with Cu(2+), Zn(2+) rescued primary cortical and human embryonic kidney 293 cells that were exposed to Abeta1-42, correlating with the effect of Zn(2+) in suppressing Cu(2+)-dependent H(2)O(2) formation from Abeta1-42. Since plaques contain exceptionally high concentrations of Zn(2+), we examined the relationship between oxidation (8-OH guanosine) levels in AD-affected tissue and histological amyloid burden and found a significant negative correlation. These data suggest a protective role for Zn(2+) in AD, where plaques form as the result of a more robust Zn(2+) antioxidant response to the underlying oxidative attack.

Aged↗