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Biomedical subjects

J Scott

Publications and source records attributed to J Scott.

At least 217 records · Page 12Linked to original sources
PubMed1997

A single photon emission computed tomography scan study of striatal dopamine D2 receptor binding with 123I-epidepride in patients with schizophrenia and controls.

The usefulness of 123I-epidepride as a single photon emission computed tomography (SPECT) scan D2 receptor ligand was examined in vivo in 13 medicated patients with schizophrenia and age- and sex-matched normal controls. To establish the effect of endogenous dopamine on 123I-epidepride binding, 4 of the 13 controls also received 20 mg D-amphetamine. The results showed that 123I-epidepride had high specific binding to the striatum in both patients with schizophrenia and normal controls. There was a trend for the total striatal binding of medicated patients with schizophrenia, as measured by total basal ganglia: frontal cortex (TBG:FC) ratios, to be less than the binding of controls (P = 0.053). This trend confirms previous work showing that antipsychotic medication decreases the number of D2 receptors available for binding to the radioligand. Interestingly, there was also a significant relationship between 123I-epidepride binding ratios and global functioning scales (Global Assessment of Functioning scale [GAF]) for schizophrenia (r = 0.56, P = 0.045), although there was no such relationship with the Brief Psychiatric Rating Scale (BPRS). In addition, our results showed that amphetamine-induced dopamine release did not alter 123I-epidepride binding, confirming the high specific binding of 123I-epidepride to the D2 receptor. We conclude that 123I-epidepride appears to be a very useful SPECT ligand for imaging the D2 receptor.

Adult↗
PubMed1997

Amino terminus of apolipoprotein B suffices to produce recognition of malondialdehyde-modified low density lipoprotein by the scavenger receptor of human monocyte-macrophages.

Malondialdehyde, a product of lipid peroxidation, produces threshold conversion of low density lipoprotein (LDL) to a form recognized by type I and type II scavenger receptors of monocyte-macrophages. To investigate whether localized domains of human apoB-100 protein provide recognition determinants, we tested the ability of several different apoB-bearing particles to interact with the scavenger receptor of human monocyte-macrophages. Genetically engineered, carboxyl-terminally truncated apoB proteins assembled into lipoprotein form were labeled by fluorescent dye. Fluorescence microscopy and quantitative fluorescent spectrophotometry showed that purified particles containing as little as 23% of the apoB amino-terminus were internalized by the scavenger receptor after, but not before, malondialdehyde modification. There was no recognition of the particles by the LDL receptor. Similar results were obtained with human plasma LDL homozygous for carboxyl-terminally truncated apoB-45.2. Liposome-incorporated fusion protein containing apoB residues 547-735 displayed specific uptake by the scavenger receptor without modification by malondialdehyde. In contrast, fusion proteins containing apoB residues 3,029-3,133 or a short amino terminal segment failed to interact. Thus, primary sequence presented by residues 1-1,084 sufficed to produce recognition of modified LDL by the scavenger receptor. These receptor-combining domains were sequestered when secreted in lipoprotein form and were expressed upon malondialdehyde modification. When packaged exogenously in liposome form, fusion protein containing apoB residues 547-735, containing approximately 4% of the primary sequence, mediated scavenger receptor-dependent uptake and hydrolysis. Our findings provide an additional function or the amino-terminal region of apoB and demonstrate that primary sequence presented by the first 2% of apoB-100 protein suffices to produce recognition on malondialdehyde-modified LDL by the scavenger receptor of human monocyte-macrophages.

Amino Acid Sequence↗
PubMed1997

A process: development of a model multiculturalism curriculum designed for mobility across geographic borders.

The Council on Accreditation Project, Nurse Anesthesia Educational Requirements and Mobility Between North American Free Trade Agreement (NAFTA) Countries, has as one of its outcomes the development of a model curriculum that would minimize educational barriers for mobility of nurse anesthetists across NAFTA geographical borders with a focus on the blending of professional and technical expertise with issues of human diversity and/or cultural differences. The overall long-term outcome of the project is to test a process. The manuscript discusses the process used in year III of the project to integrate cultural concepts into a nurse anesthesia model curriculum.

Accreditation↗
PubMed1996

The alpha1 and alpha2 isoforms of the AMP-activated protein kinase have similar activities in rat liver but exhibit differences in substrate specificity in vitro.

The AMP-activated protein kinase (AMPK) is a heterotrimeric complex composed of a catalytic subunit (alpha) and two regulatory subunits (beta and gamma). Two isoforms of the catalytic subunit (alpha1 and alpha2) have been identified. We show here that the alpha1- and alpha2-containing complexes contribute approximately equally to total AMPK activity in rat liver. Furthermore, expression of alpha1 or alpha2 with beta and gamma in mammalian cells demonstrates that both complexes have equal specific activity measured with the SAMS peptide. Using variant peptides, however, we show that alpha1 and alpha2 exhibit slightly different substrate preferences, which suggest that the two isoforms could play different physiological roles within the cell.

AMP-Activated Protein Kinases↗
PubMed1996

Apolipoprotein B RNA editing enzyme-deficient mice are viable despite alterations in lipoprotein metabolism.

RNA editing in the nucleus of higher eukaryotes results in subtle changes to the RNA sequence, with the ability to effect dramatic changes in biological function. The first example to be described and among the best characterized, is the cytidine-to-uridine editing of apolipoprotein B (apo-B) RNA. The editing of apo-B RNA is mediated by a novel cytidine deaminase, apobec-1, which has acquired the ability to bind RNA. The stop translation codon generated by the editing of apo-B RNA truncates the full-length apo-B100 to form apo-B48. The recent observations of tumor formation in Apobec-1 transgenic animals, together with the fact that Apobec-1 is expressed in numerous tissues lacking apo-B, raises the issue of whether this enzyme is essential for a variety of posttranscriptional editing events. To directly test this, mice were created with a null mutation in Apobec-1 using homologous recombination in embryonic stem cells. Mice, homozygous for this mutation, were viable and made apo-B100 but not apo-B48. The null animals were fertile, and a variety of histological, behavioral, and morphological analyses revealed no phenotype other than abnormalities in lipoprotein metabolism, which included an increased low density lipoprotein fraction and a reduction in high density lipoprotein cholesterol. These studies demonstrate that neither apobec-1 nor apo-B48 is essential for viability and suggest that the major role of apobec-1 may be confined to the modulation of lipid transport.

APOBEC-1 Deaminase↗
PubMed1996

A combined high-performance liquid chromatographic-microbiological assay for serum folic acid.

An assay of folic acid in human serum is described involving HPLC fractionation of deproteinized serum prior to Lactobacillus casei assay. High specific activity [3H]folic acid is added as internal standard to 1 ml serum prior to deproteinization with perchlorate and an aliquot is applied to a C18 reverse-phase HPLC column. The folic acid fraction was assayed by L. casei microtiter plate assay. Intra- and interassay variations (CV) were 5.5 and 7.5% respectively for sera (n = 10) spiked with folic acid. The percentage recovery for folic acid additions of 10 and 20 ng/liter were 105.2 and 103.7%, respectively. The lower limit of detection was 1 ng folic acid/ml serum. Folates other than folic acid and 5-methyltetrahydrofolate were not detected. The assay permitted serial measurements to be made of folates in serum following an oral dose.

Administration, Oral↗
PubMed1996

Polymerase chain reaction for the diagnosis of HIV infection in adults. A meta-analysis with recommendations for clinical practice and study design.

PURPOSE: To do a meta-analysis of studies that have evaluated the sensitivity and specificity of polymerase chain reaction (PCR) assay for the diagnosis of human immunodeficiency virus (HIV) infection in adults. Evaluating the performance of PCR is difficult because in certain clinical situations, the sensitivity or specificity of PCR may exceed those of the current reference standard tests (enzyme immunoassay followed by confirmatory Western blot analysis). Therefore, an additional goal was to develop recommendations for 1) the design of future evaluative studies of PCR and 2) the use of PCR in persons with suspected HIV infection. DATA SOURCES: Studies published between 1988 and 1994 that were identified in a search of 17 computer databases, including MEDLINE, and abstracts identified from conference proceedings. STUDY SELECTION: Studies were included if DNA amplification by PCR was done on peripheral blood mononuclear cells from adults. Ninety-six studies met the inclusion criteria. DATA EXTRACTION: Data were extracted independently by two reviewers. Study design was assessed independently by two investigators blinded to study results. RESULTS: Reported sensitivities for PCR range from 10% to 100%, and specificities range from 40% to 100%. A summary receiver-operating characteristic curve based on all 96 studies has a maximum joint sensitivity and specificity (upper left point on the curve, where sensitivity equals specificity) of 97.0% to 98.1%. If the threshold value that defines a positive PCR result is chosen so that sensitivity is higher than 98.1%, specificity will decrease to less than 98.1%. Conversely, if the threshold value that defines a positive PCR result is chosen so that specificity is greater than 98.1%, sensitivity will decrease to less than 98.1%. If sensitivity and specificity are chosen to be equal, the corresponding false-positive rate is 1.9% to 3.0%. At the maximum joint sensitivity and specificity, the positive predictive value of PCR ranges from 34% to 85% as the prevalence of HIV increases from 1.0% to 10%. We identified seven areas in which study design could be modified to 1) reduce susceptibility to bias in estimates of the sensitivity and specificity of PCR and 2) to increase the generalizability of the study results. These modifications will also help to overcome methodologic problems created by the lack of a reference standard test. CONCLUSIONS: The PCR assay is not sufficiently accurate to be used for the diagnosis of HIV infection without confirmation. Use of PCR for the diagnosis of HIV in adults should be limited to situations in which antibody tests are known to be insufficient. Future studies of PCR performance should be sufficiently large and should use adequate reference standard tests and standardized methods for the performance of PCR. Specimens should be evaluated by persons blinded to clinical status and to the results of other diagnostic tests for HIV infection.

Adult↗
PubMed1996

A meta-analytic evaluation of the polymerase chain reaction for the diagnosis of HIV infection in infants.

OBJECTIVE: To evaluate the sensitivity and specificity of the polymerase chain reaction (PCR) for the diagnosis of infection with human immunodeficiency virus (HIV) in infants. DATA SOURCES: We used studies published between 1988 and 1994 identified in a literature search of 17 databases, including MEDLINE. STUDY SELECTION: Studies were included if DNA amplification by PCR was performed on peripheral blood mononuclear cells from infants or children. DATA EXTRACTION: Two investigators independently extracted data. The study design was assessed independently by 2 investigators who were blinded to study results. DATA SYNTHESIS: Thirty-two studies met the inclusion criteria and were analyzed. The median reported sensitivity was 91.6% (range, 31%-100%), and the median specificity was 100% (range, 50%-100%). A summary receiver operating characteristic curve based on all 32 studies indicated that PCR has a maximum joint sensitivity and specificity between 93.2% and 94.9%. Subgroup analysis indicated that the joint sensitivity and specificity was significantly (P = .04) higher in older infants (98.2%) than in neonates (aged < or = 30 days; 93.3%). For infants at low risk of perinatal transmission (probability of transmission, 8.3%), the positive predictive value for PCR is 55.8% in neonates and 83.2% in older infants. A negative PCR result reduces the probability of HIV infection to less than 3%. No studies met all criteria for study design. CONCLUSIONS: Although PCR is one of the best available tests for diagnosis of HIV infection in neonates and infants, it is not definitive. Therefore, PCR should be interpreted with the aid of careful clinical follow-up examinations. The sensitivity and specificity of PCR in neonates is lower than in older infants, which results in a low positive predictive value; however, negative tests are informative. Delaying the use of PCR until after the neonatal period or repeating PCR on independent samples obtained 30 to 60 days later will reduce test errors.

Algorithms↗
PubMed1996

Characterization of AMP-activated protein kinase beta and gamma subunits. Assembly of the heterotrimeric complex in vitro.

There is growing evidence that mammalian AMP-activated protein kinase (AMPK) plays a role in protecting cells from stresses that cause ATP depletion by switching off ATP-consuming biosynthetic pathways. The active form of AMPK from rat liver exists as a heterotrimeric complex and we have previously shown that the catalytic subunit is structurally and functionally related to the SNF1 protein kinase from Saccharomyces cerevisiae. Here we describe the isolation and characterization of the two other polypeptides, termed AMPKbeta and AMPKgamma, that together with the catalytic subunit (AMPKalpha) form the active kinase complex in mammalian liver. Sequence analysis of cDNA clones encoding these subunits reveals that they are related to yeast proteins that interact with SNF1, providing further evidence that the regulation and function of AMPK and SNF1 have been conserved throughout evolution. The amino acid sequence of the beta subunit is most closely related to SIP2 (35% identity), while the amino acid sequence of the gamma subunit is 35% identical with SNF4. We show that both AMPKbeta and AMPKgamma mRNA and protein are expressed widely in rat tissues. We show that AMPKbeta interacts with both AMPKalpha and AMPKgamma in vitro, whereas AMPKalpha does not interact with AMPKgamma under the same conditions. These results suggest that AMPKbeta mediates the association of the heterotrimeric AMPK complex in vitro, and will facilitate future studies aimed at investigating the regulation of AMPK in vivo.

AMP-Activated Protein Kinases↗
PubMed1996

The role of protein disulphide isomerase in the microsomal triacylglycerol transfer protein does not reside in its isomerase activity.

The microsomal triacylglycerol transfer protein (MTP), an alpha beta dimer, is obligatory for the assembly of apoB-containing lipoproteins in liver and intestinal cells. The beta subunit is identical with protein disulphide isomerase, a 58 kDa endoplasmic reticulum luminal protein involved in ensuring correct disulphide bond formation of newly synthesized proteins. We report here the expression of the human MTP subunits in Spodoptera frugiperda cells. When the alpha subunit was expressed alone, the polypeptide formed insoluble aggregates that were devoid of triacylglycerol transfer activity. In contrast, when the alpha and beta subunits were co-expressed, soluble alpha beta dimers were formed with significant triacylglycerol transfer activity. Expression of the alpha subunit with a mutant protein disulphide isomerase polypeptide in which both -CGHC- catalytic sites had been inactivated also yielded alpha beta dimers that had comparable levels of lipid transfer activity relative to wild-type dimers. The results indicate that the role of the beta subunit in MTP seems to be to keep the alpha subunit in a catalytically active, non-aggregated conformation and that disulphide isomerase activity of the beta subunit is not required for this function.

Animals↗
PubMed1996

Rare event selection of fetal nucleated erythrocytes in maternal blood by flow cytometry.

A noninvasive method of prenatal genetic diagnosis requires fetal cell selection from the maternal circulation that allows efficient recovery for analysis by fluorescence in situ hybridization (FISH). We have solved several problems that negatively affect the isolation and FISH analysis of fetal nucleated red blood cells (nRBCs) in the maternal circulation. The use of glycophorin A (Gly A) antibodies (Abs) for selection is problematic because all five monoclonal antibodies (mAbs) tested caused agglutination of non-nRBCs, thereby changing both light scatter and fluorescence properties of cells by flow cytometry. Because the number of non-nRBCs is variable after Ficoll separation, isolation of nRBCs could be compromised severely by agglutination of nucleated cells with nonnucleated cells, causing them to shift light scatter and fluorescence properties. Several methods for the removal of unwanted maternal white blood cells with CD45 mAbs were also evaluated. Magnetic bead depletion was found to interfere with FISH detection because of residual bead debris after sorting. By contrast, removal of CD45+ cells by a panning technique eliminated this problem. Positive selection methods based on CD71, CD45, and LDS-751 staining and detection of fetal cells by gamma globin expression were also analyzed. Fetal cells were detected by FISH in 11 of 19 (CD71 selection) and in 13 of 15 (gamma selection) random pregnancies. These data support the possibility of a noninvasive method for isolation and analysis of fetal cells for prenatal diagnosis.

Antigens, CD↗
PubMed1996

Cognitive therapy of affective disorders: a review.

Cognitive therapy is the most extensively researched psychological treatment for nonpsychotic, unipolar outpatient depressive disorders. Careful analysis of published outcome studies suggests that its benefits in acute depression whilst very promising have not been proven, mainly because of inadequate methodology in treatment trials. However, cognitive therapy does appear to reduce the risk of depressive relapse and may have a more durable effect than pharmacotherapy alone. This paper explores short- and long-term outcome data and reviews clinical factors, including therapists competency, that may predict outcome. The development of cognitive approaches to individuals with bipolar disorders is examined. Future areas of research, particularly the need to detect which individuals may differentially respond to cognitive therapy, are identified.

Antidepressive Agents↗
PubMed1996

Serial homicide.

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Female↗