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Biomedical subjects

J McDermott

Publications and source records attributed to J McDermott.

At least 19 recordsLinked to original sources
PubMed1998

Organization of HIV-1 capsid proteins on a lipid monolayer.

In an in vitro system that mimics the assembly of immature human immunodeficiency virus (HIV) particles, ordered arrays of HIV-1 capsid (CA) proteins encoded by the viral gag gene have been obtained by incubation of histidine-tagged capsid proteins (His-HIVCA) beneath lipid monolayers containing the nickel-chelating lipid, 1,2-di-O-hexadecyl-sn-glycero-3-(1'-2"-R-hydroxy-3'-N-(5-amino-1- carboxypentyl)iminodiacetic acid)propyl ether. The membrane-bound His-HIVCA proteins formed small crystalline arrays of primitive (p1) unit cells with dimensions of a = 74.2 A, b = 126.2 A, gamma = 89.3 degrees. The image-analyzed two-dimensional projection of His-HIVCA assemblies shows a cage-like lattice, consisting of hexamer and trimer units, surrounding protein-free cage holes. The hexamer-coordinated cage holes of 26.3-A diameter are spaced at 74. 2-A intervals: these distances, and the hexamer-trimer arrangement, are consistent with previous, lower resolution studies on immature HIV-1 virus particles produced in vivo. Additionally, HIV-1 matrix protein trimer unit structures align to the His-HIVCA trimer units such that residues previously shown to interact with the HIV-1 gp120/gp41 envelope protein complex are oriented toward the hexamer cage holes. Our results form a bridge between results from conventional methods for the analysis of HIV particle structure.

Capsid↗
PubMed1997

The fusiform face area: a module in human extrastriate cortex specialized for face perception.

Using functional magnetic resonance imaging (fMRI), we found an area in the fusiform gyrus in 12 of the 15 subjects tested that was significantly more active when the subjects viewed faces than when they viewed assorted common objects. This face activation was used to define a specific region of interest individually for each subject, within which several new tests of face specificity were run. In each of five subjects tested, the predefined candidate "face area" also responded significantly more strongly to passive viewing of (1) intact than scrambled two-tone faces, (2) full front-view face photos than front-view photos of houses, and (in a different set of five subjects) (3) three-quarter-view face photos (with hair concealed) than photos of human hands; it also responded more strongly during (4) a consecutive matching task performed on three-quarter-view faces versus hands. Our technique of running multiple tests applied to the same region defined functionally within individual subjects provides a solution to two common problems in functional imaging: (1) the requirement to correct for multiple statistical comparisons and (2) the inevitable ambiguity in the interpretation of any study in which only two or three conditions are compared. Our data allow us to reject alternative accounts of the function of the fusiform face area (area "FF") that appeal to visual attention, subordinate-level classification, or general processing of any animate or human forms, demonstrating that this region is selectively involved in the perception of faces.

Adult↗
PubMed1997

Structural analysis of membrane-bound retrovirus capsid proteins.

We have developed a system for analysis of histidine-tagged (His-tagged) retrovirus core (Gag) proteins, assembled in vitro on lipid monolayers consisting of egg phosphatidylcholine (PC) plus the novel lipid DHGN. DHGN was shown to chelate nickel by atomic absorption spectrometry, and DHGN-containing monolayers specifically bound gold conjugates of His-tagged proteins. Using PC + DHGN monolayers, we examined membrane-bound arrays of an N-terminal His-tagged Moloney murine leukemia virus (M-MuLV) capsid (CA) protein, His-MoCA, and in vivo studies suggest that in vitro-derived His-MoCA arrays reflect some of the Gag protein interactions which occur in assembling virus particles. The His-MoCA proteins formed extensive two-dimensional (2D) protein crystals, with reflections out to 9.5 A resolution. The image-analyzed 2D projection of His-MoCA arrays revealed a distinct cage-like network. The asymmetry of the individual building blocks of the network led to the formation of two types of hexamer rings, surrounding protein-free cage holes. These results predict that Gag hexamers constitute a retrovirus core substructure, and that cage hole sizes define an exclusion limit for entry of retrovirus envelope proteins, or other plasma membrane proteins, into virus particles. We believe that the 2D crystallization method will permit the detailed analysis of retroviral Gag proteins and other His-tagged proteins.

Amino Acid Sequence↗
PubMed1997

Interrelationships between herd management practices and udder health status using canonical correspondence analysis.

The relationships between the herd-level distribution of udder health measures (traumatic, physical, functional and congestive udder disorders, clinical mastitis and somatic cell counts (SCC) greater than 400 x 10(3) ml-1) and farm (general hygiene, milking practices and housing system) and aggregated individual characteristics were studied by canonical correspondence analysis (CCA). This is a correspondence-analysis technique in which the axes representing disease patterns are expressed as linear combinations of potentially explanatory variables. These main axes can be drawn so that the distribution of diseases for combinations of the main-explanatory managerial variables can be visualized. The type of quarantine for newcomers, type of animal housing, presence of shelter at pasture, use of udder towel before milking, milk production and loss of body condition after calving, were strongly correlated with udder health status. Mastitis and physical udder disorders were associated with the combination of no introduction of replacement heifers and low loss of body condition after calving. Congestive disorders were more common on farms when no quarantine for newcomers was combined with high loss of body condition after calving. Higher clinical and subclinical mastitis incidence risks were associated with the combination of no udder towel, loose housing with high animal density and high milk production. In most cases, clinical mastitis and high SCC were explained by the same covariates but with contrasting levels of those covariates.

Animal Husbandry↗
PubMed1997

Evaluation of prenatal care information on birth certificates.

Misclassification frequently leads to bias in epidemiological studies, and causes concern for perinatal epidemiologists interested in using birth certificates as a data source. We used a maximum likelihood method to estimate the classification probabilities (conditional probabilities that indicate the probability of classification in a particular category, given the person's true category) of two data sources for a three-category outcome of prenatal care. The probability that women receiving adequate or inadequate care were correctly classified was estimated to be greater than 90%. The probability was much lower (< 35%) that women receiving intermediate care were correctly classified. The misclassification women from the intermediate category resulted in poor predictive values (< 70%) of women classified as receiving either adequate or inadequate care. Because of these findings, we combined the adequate and intermediate categories to form a two-category classification system. This revision resulted in higher positive predictive values (> 90%) with only a slightly lower classification probability (> 85%) for the combined category. We conclude that the degree of accuracy for a two-category classification of prenatal care based upon birth certificate information is acceptable, but we question the accuracy of indices of prenatal care with more than two categories.

Birth Certificates↗
PubMed1996

Use of magnetic resonance angiography for the preoperative evaluation of patients with infrainguinal arterial occlusive disease.

PURPOSE: This study was designed to determine whether magnetic resonance angiography (MRA) will allow preoperative management decisions without the need for contrast arteriography in patients with lower extremity ischemia caused by infrainguinal arterial occlusive disease. METHODS: Forty-five patients with lower extremity ischemia in 50 limbs were evaluated by both two-dimensional time-of-flight MRA and intraarterial digital subtraction angiography (DSA) between February 1992 and June 1995. Independent management plans were based on clinical presentation, pulse volume recordings, and separate reviews of the MRA and DSA. RESULTS: Of 50 limbs, 23 required arterial bypass, 19 percutaneous transluminal angioplasty, 5 patch angioplasty, and 3 amputation. MRA and DSA correlated exactly in 89.5% of infrainguinal arterial segments, whereas interpretations disagreed in 10.5% of arterial segments. Mismatches that had an influence on patient treatment decisions occurred in only 8 (2.3%) of 352 arterial segments. Independent MRA- and DSA-based revascularization plans agreed in 45 (90%) extremities. MRA predicted the level of arterial reconstruction in all 23 limbs that required arterial bypass. MRA identified focal stenoses amenable to percutaneous transluminal angioplasty in 18 (94.7%) of the 19 limbs that ultimately underwent percutaneous transluminal angioplasty. A strategy of preoperative planning by MRA with confirmatory intraoperative arteriography would represent a 31% cost savings per patient at our institution while eliminating the morbidity of preoperative DSA. CONCLUSIONS: When used in combination with the patient's physical examination and segmental limb pressures with plethysmography, MRA is sufficient for planning infrainguinal arterial bypass procedures and selecting patients for percutaneous transluminal angioplasty.

Aged↗
PubMed1996

Single-step PCR in molecular diagnosis of hepatitis C virus infection.

The diagnostic utility of two PCR systems and three PCR detection methods for hepatitis C virus (HCV) RNA was evaluated in serum samples. A nested PCR was considered the reference assay and was compared with two single-step PCR methods: the first is based on the detection of PCR products by liquid hybridization with a 32P-end-labeled probe, and the second is the Roche Amplicor colorimetric assay using microwell plate hybridization with a specific nucleic acid probe. Using the Pelicheck HCV RNA Eurohep genotype 1 proficiency panel, our laboratory achieved medium-high levels of performance with all three methods. The highest sensitivity was, however, observed with the isotopic single-step PCR (ss-PCR) method. The analytical sensitivity of ss-PCR with isotopic detection and ss-PCR with colorimetric detection was identical to that of nested PCR, with a 100% result concordance. Comparison of ss-PCR with enzyme-linked immunosorbent and RIBA assays in the analysis of clinical samples showed a high concordance. ss-PCR methods appear more suitable for diagnostic application. Nevertheless, HCV RNA PCR cannot be considered a screening assay; it should be requested in the presence of reactive serology or specific clinical symptomatology with altered liver parameters, and it is a potential tool for the follow-up of patients with HCV infection.

Base Sequence↗
PubMed1996

Structural analysis of human immunodeficiency virus type 1 Gag protein interactions, using cysteine-specific reagents.

We have examined structural interactions of Gag proteins in human immunodeficiency virus type 1 (HIV-1) particles by utilizing cysteine mutagenesis and cysteine-specific modifying reagents. In immature protease-minus but otherwise wild-type (wt) particles, precursor Pr55Gag proteins did not form intermolecular cystines naturally but could be cross-linked at cysteines, and cross-linking appeared to occur across nucleocapsid (NC) domains. Capsid (CA) proteins in wt mature viruses possess cysteines near their carboxy termini at gag codons 330 and 350, but these residues are not involved in natural covalent intermolecular bonds, nor can they be intermolecularly cross-linked by using the membrane-permeable cross-linker bis-maleimido hexane. The cysteine at gag codon 350 (C-350) is highly reactive to thiol-specific modifying reagents, while the one at codon 330 (C-330) appears considerably less reactive, even in the presence of ionic detergent. These results suggest that the HIV-1 CA C terminus forms an unusually stable conformation. Mutagenesis of C-350 to a serine residue in the mutant C350S (C-350 changed to serine) virtually eliminated particle assembly, attesting to the importance of this region. We also examined a C330S mutant, as well as mutants in which cysteines were created midway through the capsid domain or in the C-terminal section of the major homology region. All such mutants appeared wt on the basis of biochemical assays but showed greatly reduced infectivities, indicative of a postassembly, postprocessing replicative block. Interestingly, capsid proteins of mature major homology region mutant particles could be cysteine cross-linked, implying either that these mutations permit cross-linking of the native C-terminal CA cysteines or that major homology regions on neighbor capsid proteins are in close proximity in mature virions.

Animals↗
PubMed1996

Perinatal mortality in rural Malawi.

Reported are the results of a study to assess the prevalence and risk factors for perinatal death among pregnant women in Malawi over the period 1987-90. There were 264 perinatal deaths among the 3866 women with singleton pregnancies (perinatal mortality rate, 68.3 per 1000 births). Among the risk factors for perinatal mortality were the following: reactive syphilis serology, nulliparity, a late fetal or neonatal death in the most recent previous birth, maternal height < 150 cm, home delivery, and low socioeconomic status. Although unexplained perinatal deaths will continue to occur, perinatal mortality can be reduced if its causes and risk factors in a community are given priority in antenatal and intrapartum care programmes. The following interventions could potentially reduce the perinatal mortality in the study population: screening and treating women with reactive syphilis serology; and management from early labour, by competent personnel in a health facility, of nulliparous women and multiparous women who are short or have a history of a perinatal death.

Body Height↗
PubMed1995

The first step.

Explore the source record for details and available documents.

Health Care Reform↗
PubMed1995

The effect of a carbohydrate-rich beverage on mood, appetite, and cognitive function in women with premenstrual syndrome.

OBJECTIVE: To test the efficacy of a specially-formulated, carbohydrate-rich beverage (one known to increase the serum ratio of tryptophan to other large neutral amino acids) on the mood, cognitive, and appetitive disturbances of premenstrual syndrome (PMS). METHODS: Twenty-four women with confirmed PMS were enrolled in a double-blind, crossover study to test the efficacy of the specially-formulated beverage compared with two other isocaloric products on PMS symptoms. The study was conducted over three menstrual cycles preceded by a 1-month placebo run-in. Patients were tested at home or work using an interactive computer-telephone system. Standardized measurements of mood, cognitive performance, and food cravings were made before and 30, 90, and 180 minutes after consumption of active and placebo beverages during the late luteal phase of the menstrual cycle. RESULTS: The experimental carbohydrate intervention significantly decreased self-reported depression, anger, confusion, and carbohydrate craving 90-180 minutes after intake. Memory word recognition was also improved significantly compared with scores obtained during the placebo run-in month (P < .05). The isocaloric placebo interventions had no significant effect on any of these measures. CONCLUSION: The results suggest that the psychological and appetitive symptoms of PMS can be relieved after consuming a specially-formulated, carbohydrate-rich beverage known to increase serum tryptophan levels.

Adult↗
PubMed1995

Efficacies of dexfenfluramine and fluoxetine in preventing weight gain after smoking cessation.

We tested whether 14 wk of dexfenfluramine (30 mg) or fluoxetine (40 mg) treatment would prevent weight gain after subjects quit smoking. Normal-weight women (n = 144) were randomly assigned to drug or placebo on a double-blind basis for 2 wk before quitting smoking and 12 wk thereafter. The fluoxetine group had more dropouts (28/49, 57.1%) than the dexfenfluramine group (17/47, 36.2%), with an intermediate number of dropouts from the placebo group (21/48, 43.8%). All groups gained weight during treatment, but their amount and pattern of weight gain differed. In the first month after quitting smoking, the placebo group gained more weight than either the dexfenfluramine or fluoxetine group (P < 0.05). By 2 mo postcessation, dexfenfluramine still suppressed weight gain in comparison with placebo (P < 0.05); weight gain with fluoxetine was not differentiable from either dexfenfluramine or placebo. By 3 mo postcessation, the dexfenfluramine group had gained 1.0 +/- 0.7 kg, significantly less than either the placebo (3.5 +/- 0.7 kg) or fluoxetine (2.7 +/- 0.5 kg) groups. Three months after drug discontinuation, formerly medicated, but not placebo patients, showed additional weight gain, eliminating differences between groups. Results indicate that weight gain, an adverse accompaniment of smoking cessation, can be minimized to some degree by serotoninergic drugs, although only for the duration of drug treatment.

Adult↗
PubMed1994

The voices of reform. The final stretch. Interview by Renee Blankenau.

Following a complex research and development process last year that led to the drafting of a comprehensive health care reform proposal, President Bill Clinton presented the U.S. Congress and the nation with an outline for reform in September, and followed up with a detailed plan and with a reform bill in October. Now it's Congress' turn to respond. Hospitals & Health Networks' senior editor Renee Blankenau interviewed 11 members of Congress whose views represent a broad spectrum of congressional opinion. What version of federal reform will emerge this year? These legislators have the inside track.

Forecasting↗
PubMed1994

DNA markers linked to Malus floribunda 821 scab resistance.

Breeding resistant apple plants is an alternative way to control fungal pathogens reducing the environmental impact due to the use of pesticides. The breeding of apple cultivars resistant to Venturia inaequalis could be much improved by marker-assisted selection. A molecular marker closely linked to the resistance locus called Vf could replace selection based on infection studies. To find such molecular markers, DNA of progenies from crossings of a resistant and a susceptible apple tree was subject to bulked segregant analysis. Two markers were found with a genetic distance of 10.6% and 19.7% recombination frequency to the Vf locus.

DNA Primers↗
PubMed1994

Synthesis of the enantiomers of [N-methyl-11C]PK 11195 and comparison of their behaviours as radioligands for PK binding sites in rats.

The enantiomers of [N-methyl-11C]PK 11195, a radioligand for PET studies of PK (peripheral benzodiazepine) binding sites, have been prepared from the newly synthesized N-desmethyl-enantiomers by 11C-methylation with N.C.A. [11C]iodomethane. The brain uptake and retention of each enantiomer was compared with that of the racemic radioligand after i.v. administration into normal rats and into rats with focal cortical lesions. No significant differences in the uptakes of the enantiomers were observed in regions devoid of PK binding sites. However, the R-enantiomer was retained to a significantly greater extent than the S-enantiomer in olfactory bulbs-tubercles, which contain some PK binding sites, and also in 9-day-old focal cortical lesions, which are greatly enriched in PK binding sites associated with macrophage infiltration. The observed differences are consistent with the approximately 2-fold greater affinity of the R-enantiomer for PK binding sites reported in vitro and imply that the use of this enantiomer would have advantages over the use of the racemate currently used for PET studies.

Animals↗