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Biomedical subjects

D McDonald

Publications and source records attributed to D McDonald.

At least 55 records · Page 3Linked to original sources
PubMed1998

Invasion by Salmonella typhimurium induces increased expression of the LMP, MECL, and PA28 proteasome genes and changes in the peptide repertoire of HLA-B27.

We have analyzed proteasomal adaptation and associated changes in the B27-bound peptide repertoire in response to cellular invasion with Salmonella. The peptide repertoire of HLA-B27 complexes was analyzed by two different methods: (i) high-pressure liquid chromatography (HPLC) profiles of newly synthesized peptides eluted from B27 following metabolic labeling with arginine and (ii) reactivities with two B27 monoclonal antibodies, Ye-2 and B27.M2, sensitive to peptide-induced conformational changes. LMP, MECL, and PA28 expression was analyzed by reverse transcription-PCR (RT-PCR) of mRNA and by Western blot analysis for LMP2. Invasion of HLA-B27-transfected HeLa cells by Salmonella typhimurium induced significant changes in the reactivities of HLA-B27 with these two antibodies, which was accompanied by significant quantitative and qualitative changes in the HPLC profile of peptides eluted from HLA-B27. We also observed increases in the RT-PCR values for the LMP2, LMP7, and MECL proteasome subunit genes, as well as the proteasomal activator PA28alpha and -beta genes, and increased expression of the LMP2 protein by Western blotting. Upregulation of LMP2, but not LMP7, gene expression showed a close correlation with the changes in antibody reactivities observed upon bacterial invasion. We observed similar changes in reactivity with the Ye-2 or the B27.M2 antibody of lymphoblastoid cells upon gamma interferon treatment, which significantly correlated with the increased RT-PCR values for the LMP2 gene. This was accompanied by consistent HPLC profile changes for eluted peptides. Thus, Salmonella invasion leads to serologically recognizable changes in the B27-bound peptide repertoire, which may include peptides of host origin potentially through modulation of proteasome LMP2 subunit expression and, as a consequence, proteasomal activities.

Antigen Presentation↗
PubMed1998

Immunological and virological analyses of persons infected by human immunodeficiency virus type 1 while participating in trials of recombinant gp120 subunit vaccines.

We have studied 18 participants in phase I/II clinical trials of recombinant gp120 (rgp120) subunit vaccines (MN and SF-2) who became infected with human immunodeficiency virus type 1 (HIV-1) during the course of the trials. Of the 18 individuals, 2 had received a placebo vaccine, 9 had been immunized with MN rgp120, and seven had been immunized with SF-2 rgp120. Thirteen of the 18 infected vaccinees had received three or four immunizations prior to becoming infected. Of these, two were placebo recipients, six had received MN rgp120, and five had received SF-2 rgp120. Only 1 of the 11 rgp120 recipients who had multiple immunizations failed to develop a strong immunoglobulin G antibody response to the immunogen. However, the antibody response to rgp120 was transient, typically having a half-life of 40 to 60 days. No significant neutralizing activity against the infecting strain was detected in any of the infected individuals at any time prior to infection. Antibody titers in subjects infected despite vaccination and in noninfected subjects were not significantly different. Envelope-specific cytotoxic T-lymphocyte responses measured after infection were infrequent and weak in the nine vaccinees who were tested. HIV-1 was isolated successfully from all 18 individuals. Sixteen of these strains had a non-syncytium-inducing (NSI) phenotype, while two had a syncytium-inducing (SI) phenotype. NSI strains used the CCR5 coreceptor to enter CD4+ cells, while an SI strain from one of the vaccinees also used CXCR4. Viruses isolated from the blood of rgp120 vaccinees were indistinguishable from viruses isolated from control individuals in terms of their inherent sensitivity to neutralization by specific monoclonal antibodies and their replication rates in vitro. Furthermore, genetic sequencing of the env genes of strains infecting the vaccinees did not reveal any features that clearly distinguished these viruses from contemporary clade B viruses circulating in the United States. Thus, despite rigorous genetic analyses, using various breakdowns of the data sets, we could find no evidence that rgp120 vaccination exerted selection pressure on the infecting HIV-1 strains. The viral burdens in the infected rgp120 vaccine recipients were also determined, and they were found to be not significantly different from those in cohorts of placebo-vaccinated and nonvaccinated individuals. In summary, we conclude that vaccination with rgp120 has had,to date, no obvious beneficial or adverse effects on the individuals we have studied.

AIDS Vaccines↗
PubMed1997

Alcohol in the South Pacific: the mid-1990s.

In the mid-1990s data were obtained on alcohol consumption in the Cook Islands, Fiji, Kiribati, Samoa, the Solomon Islands and Tonga. These data are reported together with a discussion of the nature of alcohol related problems in the island nations. Per capita consumption is highest in the Cook Islands, which compared with other countries has the highest ratio of liquor outlets and lowest alcohol taxation regime. As an alcohol problem prevention measure, it is concluded that the promotion of responsible consumption, together with the option of abstinence for those who wish it, is an acceptable strategy for the Pacific.

Journal Article↗
PubMed1997

Large bowel obstruction: a postoperative complication after laparoscopic bilateral inguinal hernia repair.

Each year in the United States alone over 500,000 inguinal herniorrhaphies are performed. Numerous techniques and methods have been described, all in an attempt to decrease recurrences, complications, and morbidity. One of the newer methods involves laparoscopic, transabdominal, preperitoneal placement of a mesh sheet. Several articles have described complications following this procedure--some inherent in all hernia repairs and some unique to either the laparoscopic approach or mesh placement. Our case appears to represent the first description of a large bowel obstruction secondary to an intense, inflammatory reaction to the inserted mesh. It suggests that mesh insertion, despite reperitonealizing the mesh, is not without complication.

Hernia, Inguinal↗
PubMed1997

Collagen fibril diameters in the rabbit medial collateral ligament scar: a longer term assessment.

Previous transmission electron microscopic investigations of collagen fibril diameters in rabbit medial collateral ligament (MCL) scars have indicated a homogeneous population of small fibrils for the first 40 weeks of healing. In this study, four 8 mm MCL gap scars were studied at 78 weeks of healing and another three at 104 weeks. Results showed increased heterogeneity in the distribution of fibril diameters in all scars, with the appearance of progressively slightly larger fibrils in 78 and 104 week specimens. All longer term scars still contained roughly 90% small fibrils plus some "patches" of larger fibrils, but there was considerable variation between animals in these proportions. No scar contained the fibril populations typical of uninjured adult rabbit MCLs. These results suggest slow but on-going collagen fibril turnover and remodeling in this gap healing rabbit MCL model via currently unidentified mechanisms.

Animals↗
PubMed1997

Comparison of motion correction algorithms for cardiac SPECT.

UNLABELLED: Patient motion remains a significant source of unsatisfactory cardiac SPECT examinations. The extent to which image recovery can be achieved with correction algorithms is unknown. METHODS: Nine subjects who had completed motion-free redistribution 201Tlcardiac SPECT subsequently underwent simultaneous dual-isotope (201Tl/99mTc) SPECT with a 99mTc cutaneous point source, while the imaging table was subjected to predefined nonreturning y-translation movements. Cardiac reconstructions, marker reconstructions and marker-compressed dynamic images were generated from the raw data after applying the following correction methods: diverging squares, cross-correlation of the cardiac data and cross-correlation of the marker. RESULTS: Marker cross-correlation performed significantly better than all other methods with good-excellent results in all evaluations. This compared with good-excellent results in none of 27 for the raw data, in 13 of 27 for cardiac cross-correlation and in 7 of 27 for diverging squares (p < 10(-5)). The superiority of the marker-based method was confirmed on analysis of bullseye difference maps and quantitation of residual motion in the point-source data. CONCLUSION: Motion artifacts can accurately be detected and corrected using cross-correlation of an external point-source. Furthermore, this technique provides useful independent information on the degree of image recovery.

Algorithms↗
PubMed1996

Chronic recurrent multifocal osteomyelitis: an evolving clinical and radiological spectrum.

OBJECTIVE: To describe unusual clinical and radiological features in patients with chronic recurrent multifocal osteomyelitis (CRMO). DESIGN AND SUBJECTS: Based on radiographic and microscopic findings, three patients were prospectively diagnosed as having chronic recurrent multifocal osteomyelitis (CRMO). They form the basis of this report because of either the unusualness of the clinical presentation, hitherto undescribed associated diseases or the unusual age of presentation and sites of lesions. RESULTS: One patient developed pyoderma gangrenosum at the site of one of the skeletal lesions and then went on to develop ulcerative proctitis. A second patient presented with a soft tissue mass, which on MRI mimicked a sarcoma. The final patient presented with lesions in the wrist and phalanges of the toes at the unusual age of 38. None of the patients was treated with steroids or antibiotics for the skeletal lesions. Steroids were administered to one patient for treatment of pyoderma gangrenosum. CONCLUSIONS: The pattern and distribution of skeletal lesions in CRMO are well recognized in the pediatric age group. The unusual clinical and/or radiological features discussed herein suggests that this is a disease that continues to evolve with a broader spectrum of features than recognized.

Adult↗
PubMed1996

Surface osteomas of the appendicular skeleton.

OBJECTIVE: This study describes the radiographic, CT, and MR imaging features of surface osteomas of the appendicular skeleton in four patients without Gardner's syndrome or tuberous sclerosis and reviews the incidence and management options of this uncommon tumor. CONCLUSION: On imaging (best seen on CT), the osteomas were homogeneously dense-as dense at the periphery as the base-and without an accompanying soft-tissue mass, cortical destruction, or intramedullary invasion. The margins of each osteoma were smooth or smoothly lobulated. When the correct diagnosis was considered in two patients, close clinical follow-up or marginal excision were the management options chosen. Histologic examination of the tumors revealed dense sclerotic lamellar bone with haversian systems that showed features similar to those of normal cortical bone. During a follow-up period of 6 months to 5 years, patients have had no local recurrences or metastases.

Adult↗
PubMed1995

Rabbit medial collateral ligament scar weakness is associated with decreased collagen pyridinoline crosslink density.

This study was carried out to quantify the potential associations between material strength and both collagen concentration and pyridinoline collagen crosslink density in the healing medial collateral ligament of the rabbit and to compare these parameters with those of normal ligaments. The right hindlimbs of 24 skeletally mature (12-month-old) New Zealand White rabbits were subjected to a standardized 4 mm midsubstance "gap" injury to the medial collateral ligament. The animals were killed in groups of six at postoperative intervals of 3, 6, 14, or 40 weeks, and the femur-medial collateral ligament-tibia complexes were mechanically tested in tension to failure. Subsequent to mechanical testing, the failure sites of the ligaments were assessed for concentrations of hydroxyproline and hydroxylysyl pyridinoline. Nine additional rabbits served as age-matched normal controls. In healing ligaments, normal collagen concentrations were reached in less than 14 weeks, but the hydroxylysyl pyridinoline crosslink densities remained low and were only 45% of the control values after 40 weeks of healing. Similarly, mechanical values remained much less than the controls. Linear regression analysis of data on scar tissue alone showed a moderately strong positive correlation between hydroxyproline concentration and material strength (r2 = 0.51, p = 0.0001) but no correlation between crosslink density and strength of scar tissue. A similar pattern of correlation was obtained between the elastic modulus of the scar tissue and the biochemical variables, but the r2 values were lower.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1995

External reference markers for the correction of head rotation in brain single-photon emission tomography.

Accurate reorientation of brain single-photon emission tomography (SPET) is required for quantitative procedures and for correlation with other imaging modalities. Traditionally, brain SPET has utilized reoriented slices parallel to the orbitomeatal line (OML). Reorientation using internal landmarks would be more convenient but has not been systematically compared with the use of external landmarks. We compared the interobserver reproducibility for defining the sagittal and coronal angular deviations using internal landmarks, a visual method based upon external reference markers, and an automated method based upon external reference markers. Internal landmarks were inaccurate for defining the OML whether this was based upon the frontal-occipital or frontal-cerebellar plane. External reference markers resulted in significantly lower interobserver differences for both sagittal and coronal reorientation. An operator-independent implementation proved to be feasible and provided an objective measure of marker coplanarity. In summary, external reference markers should be used when reproducible reorientation and ROI placement are required.

Brain↗
PubMed1995

Isolation of dihydrofolate and folylpolyglutamate synthetase activities from Neurospora.

The possible association of dihydrofolate synthetase (DHFS) and folylpolyglutamate synthetase (FPGS) in Neurospora crassa (FGSC 853, wild type) has been examined using mycelial extracts prepared and fractionated in the presence of protease inhibitors. DHFS and FPGS were assayed by following the incorporation of labelled glutamate into dihydrofolate and methylenetetrahydrofolate polyglutamate, respectively. Both of these activities were predominately cytosolic in mycelia that were harvested 24 hr after spore inoculation of defined minimal medium. Relatively small amounts of total mycelial DHFS activity were associated with mitochondrial fractions isolated by differential centrifugation. In contrast, ca 20% of the mycelial FPGS activity was mitochondrial. Treatment of the mitochondrial fractions with Triton X-100 suggested that these activities were not latent under the assay conditions employed. Separate peaks of DHFS and FPGS activity were observed when (NH4)2SO4-fractionated protein was desalted and chromatographed on columns of either Mono Q HR, DEAE-cellulose, heparin agarose, Matrex Green A or Reactive Green 5. Gel filtration indicated average Mr values of 52 and 66 x 10(3) for DHFS and FPGS protein, respectively. Dihydrofolate synthetase protein was purified over 1000-fold by a protocol that included chromatography on DEAE-cellulose, DEAE-Sephacel, heparin agarose and Matrex Green A. The isolated protein lacked ability to glutamyl conjugate 5,10-methylene tetrahydrofolate. SDS-polyacrylamide gel electrophoresis of the Matrex Green A peak fractions revealed a major protein band of average Mr 52 x 10(3) whose concentration appeared to parallel DHFS activity. FPGS protein (average Mr 66 x 10(3)), which lacked ability to glutamyl conjugate dihydropteroate, was recovered by a similar protocol.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromatography, Ion Exchange↗