Committing the AMA to quality in Australian health care.
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Australia↗
Biomedical subjects
D Brand
Publications and source records attributed to D Brand.
Comparison of antibody responses to different forms of HIV-1 core antigens by epitope mapping.
The specificity of antibodies to HIV-1 capsid (p24CA) and matrix (p17MA) proteins, produced in mice against unprocessed immature assembled polyprotein (wild-type p55 virus-like particles or chimeric p55 virus-like particles) or against the monomeric mature form (rp24CA/rp17MA), was analyzed by a microplate epitope mapping assay using a panel of synthetic peptides covering the entire p24CA plus p17MA sequences of HIV-1LAI. All immunized mice developed anti-p24CA and anti-p17MA antibodies, although the spectrum of specificity of these antibodies was different. Four p24 CA epitopes (residues 176-192, 201-218, 233-253, 285-304) were recognized by anti-rp24CA/rp17MA antibodies, whereas one p17MA epitope (residues 11-25) and one p24CA epitope (residues 176-192) were constantly recognized by anti-p55 virus-like particle antibodies. These results suggest a different specificity pattern of anti-p24CA and anti-p17MA antibodies depending on whether they are produced against the soluble mature form or the immature assembled form of the gag proteins.
Amino Acid Sequence↗
Assembly and immunogenicity of chimeric Gag-Env proteins derived from the human immunodeficiency virus type 1.
We evaluated the potential of the precursor Gag protein (Pr55) of the human immunodeficiency virus type 1 (HIV-1) as a carrier for the presentation of envelope epitopes. Recombinant chimeric core-envelope protein-expressing constructs were derived by deletion of regions within the gag gene, especially of regions encoding p24 capsid epitopes. Sequences encoding either the principal neutralization determinant (PND) and/or the CD4-binding domains (CD4BS) were then inserted. Deletion of residues 196-226 within the p24 capsid protein did not prevent self-assembly into virus-like particles (VLPs) whereas deletion of residues 299-328 completely abolished VLP formation. Thus the major homology region (MHR) and proximal sequences are required for capsid assembly. An immunization study in mice showed that assembled chimeric proteins elicited strong anti-Gag, weak anti-envelope, and no neutralizing humoral responses. Nonassembled chimeric proteins were poor immunogens. Mapping of Pr55 antigenic sites using sera from immunized mice and peptides overlapping the entire Gag precursor showed that p24 capsid and p17 matrix epitopes presented to the immune system differed from the mature form (p24 or p17) and the multimeric immature form (Pr55).
Amino Acid Sequence↗
Variability of femoral muscle attachments.
Analytical and experimental models of the musculoskeletal system often assume single values rather than ranges for anatomical input parameters. The hypothesis of the present study was that anatomical variability significantly influences the results of biomechanical analyses, specifically regarding the moment arms of the various thigh muscles. Insertions and origins of muscles crossing or attaching to the femur were digitized in six specimens. Muscle volumes were measured; muscle attachment area and centroid location were computed. To demonstrate the influence of inter-individual anatomic variability on a mechanical modeling parameter, the corresponding range of muscle moment arms were calculated. Standard deviations, as a percentage of the mean, were about 70% for attachment area and 80% for muscle volume and attachment centroid location. The resulting moment arms of the m. gluteus maximus and m. rectus femoris were especially sensitive to anatomical variations (SD 65%). The results indicate that sensitivity to anatomical variations should be analyzed in any investigation simulating musculoskeletal interactions. To avoid misinterpretations, investigators should consider using several anatomical configurations rather than relying on a mean data set.
Aged↗
Number of ++submissions to the Journal of Biomechanics.
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Periodicals as Topic↗
A simple procedure to generate chimeric Pr55gag virus-like particles expressing the principal neutralization domain of human immunodeficiency virus type 1.
The Pr55gag human immunodeficiency virus type 1 (HIV-1) precursor protein that is capable of auto-assembling was used as a carrier for a consensus sequence of the principal neutralization domain (PND) of the HIV-1 envelope. For this purpose, a modified HIV-1 gag gene with deletion of the sequence encoding a previously described p24 epitope (amino acids 196-228 of Pr55gag) was first obtained using PCR with degenerate primers, and then cloned. This deleted gag gene allowed in a second time the insertion of a synthetic oligonucleotide cassette encoding the North American/European consensus PND precisely in place of the p24 epitope. The chimeric gene was then inserted into a baculovirus transfer vector and expressed in insect cells. The construct formed 100-140 nm virus-like particles that were released into the extracellular medium. The use of a serum-free medium that supports growth of insect cells facilitated the downstream purification of the extracellular particles. The chimeric particles were recognized by monoclonal antibodies directed to V3 by Western blot but not by immune electron microscopy, suggesting that, although the inserted sequence was still antigenic it was not exposed at the surface of the particles. The results show the ability of Pr55gag to serve as a carrier for easy insertion, in a precisely defined region, of selected epitopes of gp120 surface envelope protein, and to still auto-assemble in virus-like particles. However, the data indicate that exposed epitopes of the mature p24 protein are not presented similarly in the Pr55 precursor, and therefore that different constructs with various insertions in different places must be generated. Such constructs offer an attractive approach for HIV vaccine development and will need evaluation for both antigenicity and immunogenicity.
Amino Acid Sequence↗
Determinants of human immunodeficiency virus type 1 entry in the CDR2 loop of the CD4 glycoprotein.
Various roles for the viral receptor, CD4, have been proposed in facilitating human immunodeficiency virus type 1 (HIV-1) entry, including virion binding to the target cell and the induction of conformational changes in the viral envelope glycoproteins required for the membrane fusion reaction. Here, we compare the structural requirements in the CDR2-like loop of CD4 domain 1, the major contact site of the gp120 envelope glycoprotein, for gp120 binding and virus entry. For every CD4 mutant examined, the level of cell surface expression and the gp120 binding affinity were sufficient to explain the relative ability to function as a viral receptor. The decrease in relative infectibility associated with decreased gp120 binding affinity was more pronounced at lower cell surface CD4 concentrations. These results imply that both receptor density and affinity determine the efficiency of HIV-1 entry and that specific structures in the CD4 residues examined are probably not required for HIV-1 entry functions other than gp120 binding.
CD4 Antigens↗
Frequency of early in utero HIV-1 infection: a blind DNA polymerase chain reaction study on 100 fetal thymuses.
OBJECTIVE: To estimate the prevalence of in utero transmission of HIV-1 through the second trimester. MATERIAL AND METHODS: One hundred consecutive, unselected, intact fetuses, beyond 15 weeks gestational age (mean, 22.4 weeks) were studied. These were obtained following spontaneous intrauterine deaths (n = 4), miscarriages (n = 4), and elective mid-trimester terminations (n = 92), eight of which were fetuses with malformations from HIV-1-positive pregnancies. Coded DNA extracts from the fetal thymuses were tested blindly by polymerase chain reaction in three laboratories using a total of six different primer pairs. RESULTS: Two thymuses tested positive [95% confidence interval (Cl), 0.2-7]. Results from the three laboratories were consistent in all 100 cases. The two fetuses with HIV in the thymus both tested positive in other organs, demonstrating systemic HIV infection. The first fetus, whose mother had advanced AIDS, had died in utero and had diffuse toxoplasmosis. The second died following extremely premature delivery in a pregnancy complicated by repeated bleeding. HIV infection was observed in none of the 92 fetuses that resulted from elective mid-trimester terminations (95% Cl, 0-4). CONCLUSION: The frequency of early in utero HIV infection appears to be low, compared with transmission rates in infants born to HIV-1-infected mothers, suggesting that transmission occurs mostly later in pregnancy and/or at delivery. Specific risk factors may have implications in the occurrence of early as opposed to late transmission.
Adult↗
High antigenic cross-reactivity of the V3 consensus sequences of HIV-1 gp120.
The principal neutralization determinant (PND) of the human immunodeficiency virus type 1 (HIV-1) is located within the variable V3 region of the external envelope protein gp120. Although it is recognized that V3 sequences induce antibody response with restricted neutralization activity in vitro, we observed that the V3 consensus sequences representing North American/European and African isolates were highly cross-reactive, binding 94 and 77%, respectively, of sera collected from HIV-1 individuals originating from various parts of the world. Even HIV-1-positive sera from some East African residents, infected by strains whose V3 loop sequences are undoubtedly distinct from the North American/European consensus V3 loop sequence, reacted better to the V3 North American/European consensus peptide than to African-specific V3 sequences. Results indicate that the V3 consensus sequences represent the best candidates for optimal cross-reactivity with a wide variety of strains. Furthermore, using immunoassays for antibodies to prototype-specific V3 sequences, it is shown that HIV-1 strains related to the MN group are prevalent in West Africa, indicating either a West African origin of the MN-related viruses or more probably an introduction of this group of viruses through European/North American contacts.
Africa↗
Prevalence and significance of hepatitis C virus (HCV) viremia in HCV antibody-positive subjects from various populations.
Hepatitis C virus (HCV) infection is currently assessed by detection of antibodies to HCV with immunoassays. However, in the absence of an in vitro system to isolate the virus, or an immunoassay to identify HCV antigen in blood, an ongoing acute or chronic HCV infection can be diagnosed only by detection of HCV RNA by polymerase chain reaction. We used a reverse transcription-nested polymerase chain reaction to detect an HCV 5' noncoding viral RNA sequence in serum specimens collected from anti-HCV-positive individuals belonging to different risk groups and compared the results with those obtained with a prototype recombinant immunoblot assay (Chiron HCV SIA prototype recombinant immunoblot assay [RIBA]) containing four different viral peptides (c22, c33c, c100, and NS5). The prevalence of HCV viremia ranged from 25.9% in HCV antibody-positive blood donors to 92% in HCV antibody-positive hemophiliacs. Elevated alanine aminotransferase values in HCV antibody-positive patients were clearly associated with viremia. Ninety-six percent of HCV RNA-positive patients reacted to two viral antigens or more, compared with only 64% of HCV RNA-negative patients. Contrary to previous reports, HCV viremia was not associated with either the presence or the absence of a particular antibody specificity. The newly introduced NS5 peptide did not improve the sensitivity or specificity of the RIBA. Although 20% of the patients in our study whose sera reacted to all of the antigens were HCV RNA negative, the positive predictive value of a RIBA considered positive by the manufacturer (two or more bands), was rather high (78%) and may allow suspicion of viremia in EIA2 enzyme-linked immunosorbent assay-positive patients.
Alanine Transaminase↗
Enzyme-linked oligosorbent assay for detection of polymerase chain reaction-amplified human immunodeficiency virus type 1.
An enzyme-linked oligosorbent assay (ELOSA) was developed for the detection on microtiter plates of polymerase chain reaction (PCR)-amplified human immunodeficiency virus type 1 (HIV-1) DNA. The denatured PCR product was hybridized with a passively adsorbed oligonucleotide capture probe and a horseradish peroxidase-labeled oligonucleotide detection probe. The sensitivity and specificity of the PCR-ELOSA technique depended to some extent on the nucleotide sequences of the oligonucleotide primer and probe quartet used in the amplification and detection. We evaluated five oligonucleotide quartets located in the gag, pol, vpr, env, and nef regions of HIV-1. DNAs from 39 HIV-1-seropositive individuals and 27 healthy HIV-1-seronegative controls were amplified by the PCR procedure, and the products were detected by ELOSA. Ten copies of HIV-1 DNA against a background of 1 microgram of human DNA were specifically detected by PCR-ELOSA. Specificities and sensitivities were, respectively, 100 and 95% for the gag system, 100 and 97% for the pol system, 100 and 85% for the vpr system, 96 and 95% for the env system, and 100 and 95% for the nef system. The simplicity of ELOSA makes it suitable for automation and applicable to genetic testing and detection of viral and bacterial DNAs or RNAs in most routine laboratories.
Base Sequence↗
Dying with dignity.
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History, 20th Century↗
A chest pain clinic to improve the follow-up of patients released from an urban university teaching hospital emergency department.
During a 12-month period, 1,045 of 1,554 patients (67%) over age 30 seen in an urban teaching hospital emergency department with acute chest pain were released based on the clinical judgment of the examining physician. Patients who were released were offered follow-up within 24 to 72 hours in a hospital-based chest pain clinic. Of these 1,045 patients, 772 (74%) returned or were contacted by phone, and 29 were directly admitted; 14 had unstable angina, and eight had new myocardial infarctions. Because of its positive impact on the quality of care at an acceptable cost, the Chest Pain Clinic, which was originally instituted as part of a research protocol, has now become part of the routine spectrum of care provided at the University of Cincinnati Medical Center.
Adult↗
[Value of magnetic resonance imaging in a lipoma of the left ventricle].
A patient with benign left ventricular lipoma was explored pre- and post-operatively with echocardiography, computerized tomography (CT) and magnetic resonance imaging (MRI). With MRI spin-echo sequences the lipoma emitted a bright signal similar to that of normal fatty tissue on the two echoes of the sequence (28 ms and 65 ms). MRI was not better than CT to demonstrate that the tumour was a lipoma, but it proved to be the best technique to obtain information on tumoral spread to the myocardium and pericardium, and it showed the intracavitary extension without the need for contrast medium injection. After surgery, MRI displayed the remains of a septal lipomatous lesion. This case underlines the usefulness of MRI for the evaluation of cardiac tumours, and particularly lipomas.
Echocardiography↗
Right-to-die groups seek another right: to aid in suicide.
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Euthanasia↗
Hand injuries: incidence and epidemiology in an emergency service.
During a four-month period, 1,164 patients presented to the surgical section of our Emergency Services (ES) with chief complaints involving the hand. Patient records were analyzed for several variables including demographics, diagnosis and therapeutic procedures. Lacerations were the most frequent injury, 61.5% (n=716) with deep structure injuries present in 6.1% (n=44). Of deep structure injuries, 36.4% were tendon lacerations, 27.2% were nerve injuries, and 36.4% were compound fractures. "Bites" accounted for 5.2% (37) of all lacerations, eight of which were human bites. Fractures were the second most frequent injury, (11.4%) and involved 143 separate bones. Infections were present in 7%; over half were paronychias. There were 42 (3.6%) thermal injuries.
Adolescent↗
A multicentre trial of perhexiline maleate, beta-blocker and placebo in angina pectoris.
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Adrenergic beta-Antagonists↗
Packed bed column fermenter and kinetic modeling for upgrading the nutritional quality of coffee husk in solid-state fermentation.
Studies were carried out to evaluate solid-state fermentation (SSF) for the upgradation of the nutritional quality of coffee husk by degrading the caffeine and tannins present in it. SSF was carried out by Aspergillus niger LPBx in a glass column fermenter using factorial design experiments and surface response methodology to optimize bioprocess parameters such as the substrate pH and moisture content and aeration rate. The first factorial design showed that the moisture content of the substrate and aeration rate were significant factors for the degradation of toxic compounds, which was confirmed by the second factorial design too. The kinetic study showed that the degradation of toxic compounds was related to the development of the mold and its respiration and also to the consumption of the reducing sugars present in coffee husk. From the values obtained experimentally for the oxygen uptake rate and CO(2) evolved, the system determined a biomass yield (Y(x/o)) of 3.811 (g of biomass).(g of consumed O(2))(-1) and a maintenance coefficient (m) of 0.0031 (g of consumed O(2)).(g biomass of biomass)(-1).h(-1). The best results on the degradation of caffeine (90%) and tannins (57%) were achieved when SSF was carried out with a 30 mL.min(-1) aeration rate using coffee husk having a 55% initial moisture content. The inoculation rate did not affect the metabolization of the toxic compounds by the fungal culture. After SSF, the protein content of the husk was increased to 10.6%, which was more than double that of the unfermented husk (5.2%).
Algorithms↗