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M R MacDonald

Publications and source records attributed to M R MacDonald.

At least 19 recordsLinked to original sources
PubMed1999

Spliced mRNA encoding the murine cytomegalovirus chemokine homolog predicts a beta chemokine of novel structure.

A viral mRNA of the late kinetic class expressed by murine cytomegalovirus (MCMV) contains an open reading frame (ORF) whose predicted protein, designated MCK-1, has homology to beta chemokines (M. R. MacDonald, X.-Y. Li, and H. W. Virgin IV, J. Virol. 71:1671-1678, 1997). The present study analyzed further the structure of the transcript in infected fibroblast cells. A splicing event removed the MCK-1 stop codon, bringing a downstream ORF into frame with the chemokine homolog and demonstrating that the MCK-1 ORF was an exon of a larger gene. The predicted 31.4-kDa protein, designated MCK-2, contains a putative amino-terminal signal sequence and a beta chemokine domain, followed by a carboxyl-terminal domain without significant homology to known proteins. Quantitative analysis of mRNA forms in MCMV-infected fibroblast cells at late times after infection indicated that the viral chemokine RNA was predominantly spliced. There was no evidence for expression of RNA encoding either MCK-1 or MCK-2 at immediate early or early times after infection with MCMV. Monoclonal antibodies generated against bacterially expressed MCK-2 recognized multiple proteins in the range of approximately 30 to approximately 45 kDa in Western blot analysis of MCK-2 expressed in transfected COS cells. The monoclonal antibodies immunoprecipitated a similar group of proteins in transfected COS cells metabolically labeled with radioactive cysteine. Radiolabelled protein of apparent higher molecular mass was immunoprecipitated from culture medium overlying the transfected cells, suggesting that posttranslationally modified MCK-2 can be secreted. Two proteins with apparent molecular mass suggestive of posttranslational modification were detected by Western blot analysis of cells harvested at late times after infection with MCMV. These studies show that MCMV encodes and expresses a beta chemokine homolog with a novel predicted structure.

Amino Acid Sequence↗
PubMed1998

Mucosal and parenteral vaccination against acute and latent murine cytomegalovirus (MCMV) infection by using an attenuated MCMV mutant.

We used a live attenuated murine cytomegalovirus (MCMV) mutant to analyze mechanisms of vaccination against acute and latent CMV infection. We selected MCMV mutant RV7 as a vaccine candidate since this virus grows well in tissue culture but is profoundly attenuated for growth in normal and severe combined immunodeficient (SCID) mice (V. J. Cavanaugh et al., J. Virol. 70:1365-1374, 1996). BALB/c mice were immunized twice (0 and 14 days) subcutaneously (s.c.) with tissue culture-passaged RV7 and then challenged with salivary gland-passaged wild-type MCMV (sgMCMV) intraperitoneally (i.p.) on day 28. RV7 vaccination protected mice against challenge with 10(5) PFU of sgMCMV, a dose that killed 100% of mock-vaccinated mice. RV7 vaccination reduced MCMV replication 100- to 500-fold in the spleen between 1 and 8 days after challenge. We used the capacity to control replication of MCMV in the spleen 4 days after challenge as a surrogate for protection. Protection was antigen specific and required both live RV7 and antigen-specific lymphocytes. Interestingly, RV7 was effective when administered s.c., i.p., perorally, intranasally, and intragastrically, demonstrating that attenuated CMV applied to mucosal surfaces can elicit protection against parenteral virus challenge. B cells and immunoglobulin G were not essential for RV7-induced immunity since B-cell-deficient mice were effectively vaccinated by RV7. CD8 T cells, but not CD4 T cells, were critical for RV7-induced protection. Depletion of CD8 T cells by passive transfer of monoclonal anti-CD8 (but not anti-CD4) antibody abrogated RV7-mediated protection, and RV7 vaccination was less efficient in CD8 T-cell-deficient mice with a targeted mutation in the beta2-microglobulin gene. Although gamma interferon is important for innate resistance to MCMV, it was not essential for RV7 vaccination since gamma interferon receptor-deficient mice were protected by RV7 vaccination. Establishment of and/or reactivation from latency by sgMCMV was decreased by RV7 vaccination, as measured by diminished reactivation of MCMV from splenic explants. We found no evidence for establishment of splenic latency by RV7 after s.c. vaccination. We conclude that RV7 administered through both systemic and mucosal routes is an effective vaccine against MCMV infection. It may be possible to design human CMV vaccines with similar properties.

Animals↗
PubMed1997

Marshall-Stickler phenotype associated with von Willebrand disease.

We report on 6 individuals from three different kindreds with Marshall-Stickler (MS) phenotype, with characteristic orofacial abnormalities, arthropathy, deafness, and eye findings, all of whom were discovered to have a mild bleeding diathesis and coagulation-study findings consistent with mild von Willebrand disease (vWD). MS syndrome has been linked in some cases to the type II procollagen gene (COL2A1) on chromosome 12q, and to the collagen XI gene (COL11A2) on chromosome 6. The von Willebrand factor (vWF) is encoded by a 180-Kb gene located on the short arm of chromosome 12. This is the first reported association of these two disorders.

Adolescent↗
PubMed1997

Late expression of a beta chemokine homolog by murine cytomegalovirus.

A gene (HJ1) present in murine cytomegalovirus (MCMV) encodes an open reading frame (ORF) whose predicted amino acid sequence shows homology to the beta (or C-C) class of chemotactic cytokines known as chemokines. The region of homology is located in the carboxyl-terminal portion of the 116-amino-acid ORF. A 0.9-kb RNA transcript corresponding to the HJ1 gene is expressed in MCMV-infected fibroblasts and macrophages as a member of the late kinetic class of virally encoded transcripts. A transcriptional start site is located between the third and fourth methionine residues in the ORF, predicting a primary amino acid structure, starting at the fourth methionine residue, which includes a possible signal peptide as well as conserved cysteine residues typical for mammalian beta chemokines. The RNA transcript is polyadenylated, suggesting that it can undergo translation within the cytoplasm of an MCMV-infected cell. We speculate that expression of the chemokine homolog at late times in the MCMV replication cycle plays a role in MCMV pathogenesis, possibly by action as a chemotactic agonist or antagonist or by alteration of the activation or differentiation state of a susceptible cell such as a macrophage.

Amino Acid Sequence↗
PubMed1997

Robin sequence.

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Humans↗
PubMed1997

Stickler syndrome.

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Chromosome Aberrations↗
PubMed1996

Congenital cystic adenomatoid malformation of the lung referred as 'airway foreign body'.

Congenital cystic adenomatoid malformation of the lung is an uncommon anomaly. Two patients with this condition were recently referred to the Otolaryngology Service at The Hospital for Sick Children, Toronto, Ontario, for bronchoscopic evaluation of the airway to rule out a foreign body. Although history did not disclose a clear episode of aspiration in either case, chest radiographs showed unilateral lobar hyperinflation with mediastinal shift, consistent with foreign body obstruction. We report two cases to introduce congenital cystic adenomatoid malformation to the English otolaryngology literature and to increase awareness of it among otolaryngologists.

Child, Preschool↗
PubMed1996

Wide polytef (Gore-Tex) implants in lip augmentation and nasolabial groove correction.

OBJECTIVE: To describe a new technique of polytef (Gore-Tex) implantation into the upper and lower lips and nasolabial grooves by using large implants as a method that achieves effective cosmetic improvement. SETTING: A private cosmetic surgery center. PARTICIPANTS: Thirty-three (female) patients who desired fuller lips and 62 patients (52 female and 10 male) who requested less prominent cheek lip grooves. MAIN OUTCOME MEASURE: Significant patient satisfaction after 12 to 54 months. RESULTS: Conspicuous aesthetic effect that related to both lip and nasolabial groove correction was documented. All patients but 4 (2 in each group) were pleased with the final outcome of the treatment. CONCLUSIONS: In the opinion of the authors, the threading technique of polytef implantation creates inconspicuous improvement-both in lip augmentation and nasolabial groove correction. Large polytef implants that were inserted through a tunneling technique produced consistently good results. Implants (lip augmentation: width, < or = 10 mm, and thickness, 4 mm; nasolabial groove correction: width, 8 mm, and thickness, < or = 8 mm) were found to be safe, simple, and effective.

Adult↗
PubMed1996

Murine cytomegalovirus with a deletion of genes spanning HindIII-J and -I displays altered cell and tissue tropism.

Murine cytomegalovirus (MCMV) gene products dispensable for growth in cell culture are likely to have important functions within the infected host, influencing tissue tropism, dissemination, or immunological responses against the virus. To identify such genes, our strategy was to delete large regions of the MCMV genome likely to contain genes nonessential for virus replication in NIH 3T3 cells. Mutant virus RV7 contained a deletion of 7.7 kb spanning portions of MCMV HindIII-J and -I. This virus grew comparably to wild-type (WT) virus in NIH 3T3 fibroblasts, primary embryo fibroblasts, and bone marrow macrophages. However, RV7 failed to replicate in target organs of immunocompetent BALB/c mice and severe combined immunodeficient mice, which are exquisitely sensitive to MCMV infection. This defect in vivo growth may be related to the observation that RV7 grew poorly in the peritoneal macrophage cell line IC-21, which is highly permissive for growth of WT MCMV. Two other mutant viruses with an insertion or smaller deletion in the region common to the RV7 deletion grew comparably to WT virus in the macrophage cell line and replicated in salivary gland tissue. The poor growth of RV7 in IC-21 cells was due to a block in immediate-early gene expression, as levels of RNA from immediate-early gene IE1 were reduced eightfold compared with levels for WT virus in macrophages infected with RV7. Consequently, levels of RNA from early and late genes were also reduced. The lower expression of IE1 in RV7-infected IC-21 macrophages was not due to defective entry of virus into the cells, as equal amounts of viral DNA were present in cells 3 h after infection with RV7 or WT MCMV. These studies demonstrate that deletion of sequences in HindIII-J and -I confer altered cell and tissue tropism.

3T3 Cells↗
PubMed1995

The effect of relative humidity on mouse allergen levels in an environmentally controlled mouse room.

To determine the effect of humidity on the levels of the mouse allergen Mus m 1, an experimental animal room was constructed to control environmental variables. The sex, strain, age, and number of mice was constant in the room, so that the average daily production of Mus m 1 would not vary greatly. Six different levels of relative humidity from 15% to 65% were maintained for a minimum of a week each. Daily collections of airborne particulates were eluted from filters and Mus m 1 content measured by immunological assay. Increasing relative humidity caused a decrease in Mus m 1 levels from a high of 3 ng/m3 at 15% humidity to a low of 0.5 ng/m3 at 65% humidity. Thus, reduction of airborne allergen levels can be achieved by careful attention to humidity control, especially during the winter heating season when humidity levels may be low. This experimental room can be used to measure the effect of other variables such as ventilation rate, caging, bedding, and work practices on the levels of mouse allergen in an animal facility.

Allergens↗
PubMed1995

Memory complaints in chronic pain.

OBJECTIVE: In clinical practice, patients with chronic pain frequently report problems with memory functioning. This issue, however, has received little attention in the scientific literature. The present study was designed to investigate this common problem and to stimulate research interest in this neglected and important area. DESIGN: Self-reported memory problems were investigated in two groups of chronic pain patients--patients with pain from acceleration-deceleration automobile accidents (n = 56) and patients with pain from various work accidents (n = 27)--and two control groups involving medical/dental (n = 24) and psychotherapy patients (n = 20). SETTING: Private practice, chronic pain, rehabilitation psychology services. RESULTS: Our findings suggest that memory complaints are higher in patients with chronic pain than in medical/dental or psychotherapy patients. No differences were found between chronic pain groups. On more general measures of memory complaint, differences between pain patients and controls were attributed to the severity of patients' depression. On a questionnaire designed to be more specific to memory complaint in chronic pain patients, differences in memory complaint between pain patients and controls were found, even after the effects due to depression were statistically removed. Although pain patients often attribute their memory problems to codeine use and/or psychoactive medications, there was no support for this in the present study. CONCLUSIONS: Within the limitations of this study, these findings suggest that memory complaints may be related not only to depression but also to the presence of chronic pain. Further research in this area is needed.

Adult↗
PubMed1994

Hypoplasia of the cerebellar vermis and corpus callosum in thrombocytopenia with absent radius syndrome on MRI studies.

Thrombocytopenia with absent radius (TAR) syndrome is infrequently (7%) associated with mental retardation. In those cases, the mental deficiency is presumed to be a consequence of intracranial hemorrhage due to the thrombocytopenia. We report on 2 infants with TAR syndrome. One had developmental delay with evidence of cerebral dysgenesis by magnetic resonance imaging (MRI). Such findings have not been noted in the literature, but may not have been investigated in most cases. The other infant with TAR syndrome, who has had normal psychomotor development, has a normal brain on MRI scan. Detailed neuroimaging studies, preferably MRI, should be considered in the evaluation of patients with TAR syndrome, especially when there are documented signs of developmental delay, with or without a history of intracranial hemorrhage.

Abnormalities, Multiple↗
PubMed1994

Distribution of airborne mouse allergen in a major mouse breeding facility.

BACKGROUND: Occupational allergy to mice is a major cause of disability among workers in mouse breeding and research facilities. Efforts to prevent and treat allergy require a detailed knowledge of exposure levels to allergen. OBJECTIVE: This study was designed to quantitate the level of major mouse allergen (Mus m I) in central room air and immediate breathing zones under a variety of working conditions. METHODS: An Andersen sampler (Groseby Andersen, Spirotech Div., Atlanta, Ga.) was used to collect allergen in each room. A Gillian Personal sampler (Gillian Instrument Corp., West Caldwell, N.J.) collected particles in the worker breathing zone. ELISA was used to quantitate the concentration of Mus m I collected on the two collection devices. RESULTS: Total Mus m I recovered from Andersen samplers ranged from 0.2 to 1.5 ng/m3 in rooms without mice and 0.5 to 15.1 ng/m3 in rooms with mice. Allergen recovered from the zone of worker activity ranged from 1.2 to 2.7 ng/m3 in rooms without mice and from 16.6 to 563.0 ng/m3 in rooms with mice. Direct mouse contact was associated with the highest levels of exposure to Mus m I. Analysis revealed the bulk of allergen to be in mid-particle size ranges (3.3 to 10 microns) for mouse-containing rooms and in small particle size range (0.43 to 3.3 microns) for non-mouse-containing rooms, suggesting that small particles were carried along corridors from rooms with mice into non-mouse-containing rooms. Ventilation characteristics of rooms and mouse population density were evaluated with a "mouse loading" index (number of mice per cubic meter of ventilated air per hour). Mouse loading correlated strongly with small particles (< 3.3 microns) in ambient air. CONCLUSIONS: Mus m I is widely distributed within mouse breeding facilities. Direct worker contact with mice seems to be the major factor in high level exposure.

Air Pollutants, Occupational↗
PubMed1993

Brain magnetic resonance imaging findings in the Opitz G/BBB syndrome: extension of the spectrum of midline brain anomalies.

We report the brain magnetic resonance imaging findings in 4 patients with the Opitz BBB/G syndrome. The scans were assessed by subjective interpretation and computerized image analysis. Findings noted in 3 of the 4 patients include hypoplasia or agenesis of the corpus callosum (3 patients), cerebellar vermal hypoplasia (2 patients), cortical atrophy and ventriculomegaly (3 patients), macro cisterna magna (3 patients), and a wide cavum septum pellucidum (1 patient). One patient had a normal scan. The demonstration of a wide cavum septum pellucidum extends the spectrum of midline brain anomalies (ventral induction defects) reported in this condition. This study along with other recent reports suggests that midline brain anomalies may be frequent findings in Opitz syndrome.

Adult↗
PubMed1993

New onset wheezing in an older male population: evidence of allergen sensitization in a longitudinal study. Results of the normative aging study.

BACKGROUND: Thirty-nine male subjects, with new-onset wheezing, were selected from participants in the Department of Veterans Affairs Normative Aging Study and compared with 74 age-matched controls. Wheezing was defined by responses to a standardized and regularly administered questionnaire. The subjects with wheezing had a reduced FEV1 compared with controls (p = 0.005), but most had values above 80% predicted. Current smoking was more common in subjects with wheezing (36.8% vs 8.11% in controls, p < 0.001). The mean age of both subjects and controls was 64 years. METHODS: Allergen-specific IgE antibodies were measured, starting with sera at the time of the most recent questionnaire, and on the average 3.1, 7.6, and 12.3 years before that, with use of stored serum samples. RESULTS: Total IgE did not differ significantly between the groups. IgE binding to dust mite antigen was detected in 13% to 15% of the subjects with wheezing compared with fewer than 7% of the controls over four time intervals (p = 0.014). IgE binding to cat and ragweed antigens did not differ significantly between groups. If current nonsmokers were analyzed separately, IgE binding to cat allergen was also slightly greater in subjects with wheezing compared with controls (p = 0.054). Sequential analysis of IgE antibody levels to mite antigen, over time, indicated that IgE antibody antedated the onset of wheezing. CONCLUSIONS: New-onset wheezing in an older adult male population is significantly associated with allergic sensitization to dust mite. There was a borderline association with sensitization to cat in noncurrent smokers only. This supports the hypothesis that a subgroup may have allergic triggers to their symptoms.

Adult↗