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Biomedical subjects

M MacDonald

Publications and source records attributed to M MacDonald.

At least 55 records · Page 3Linked to original sources
PubMed1994

Risk factors for hepatitis C virus infection among injecting drug users in Sydney.

OBJECTIVE: To study risk factors for hepatitis C virus (HCV) infection in injecting drug users (IDUs) from central Sydney. SETTING AND SUBJECTS: All IDUs attending a primary health care facility in central Sydney between December 1991 and November 1992 who underwent HCV antibody testing. METHODS: Information was obtained retrospectively from client forms routinely completed at the time of medical consultation. Additional information on injecting history and practice was obtained from the registration forms of subjects who also attended the needle syringe exchange programme at the same health care facility. RESULTS: Of the 201 IDUs tested, 118 (59%) had HCV antibodies, which did not differ significantly between males and females. HCV prevalence increased significantly with age, being highest in IDUs who were aged 35 years or more (93%) and lowest in IDUs aged under 20 years (17%). HCV prevalence increased significantly with time since first injecting, from 26% for IDUs who had injected for less than 3 years to 94% for those who had injected for more than 10 years. HCV prevalence was also significantly higher in heterosexual IDUs as compared with homosexual male IDUs, and in opiate users as compared with stimulant users, even after adjustment for age and duration of injecting. HCV prevalence was strongly associated with exposure to hepatitis B virus, but was not associated with exposure to HIV. CONCLUSION: Recent HCV transmission indicates ongoing injecting risk behaviour despite HIV prevention efforts, and underlies the potential for increased transmission of HIV through the sharing of injecting equipment. Within the population of IDUs, those who are heterosexual or inject heroin appear to be at increased risk of HCV infection.

Adolescent↗
PubMed1994

Research considerations: the link between housing and health in the elderly.

1. Elderly tenants of housing projects are "aging in place" and increasingly need more supportive services. 2. The link between housing and health for the elderly is not recognized. 3. Elders differ on how declining health and disability should be managed in housing projects. 4. Fostering participation in decision making is health promoting.

Activities of Daily Living↗
PubMed1994

Phase II trial of Virulizin in patients with pancreatic cancer.

Twenty-two patients were enrolled in a clinical trial to determine the toxicity and efficacy of the novel immunomodulator Virulizin in patients with measurable, biopsy-proven pancreatic cancer. The dose was 0.11 ml/kg (minimum 7.5 ml) 3 times weekly for the first week, then twice weekly until disease progression. No toxicity was encountered. In the 17 evaluable patients there was no evidence of tumour regression. Six patients (35%) had disease stabilization for more than 3 months, and 2 are still alive with progressive disease, having had disease stabilization for 15 and 17 months. While the results do not suggest any cytotoxic activity at this dose and schedule, the possibility of an antiproliferative effect warrants further study of this agent.

Adenocarcinoma↗
PubMed1993

Nature of the ribosomal mRNA track: analysis of ribosome-binding sites containing different sequences and secondary structures.

The ribosomal mRNA track was investigated by toeprinting 30S ribosomes, in the presence or absence of tRNA, using a variety of different ribosome-binding sites. We found that: (1) the ribosome, by itself, recognizes the mRNA translational initiation site; (2) the ribosomal mRNA track makes extensive contact with mRNA independent of tRNA and the start codon; (3) ribosome-mRNA complexes are less stable than complexes containing tRNA; and (4) toeprinting can be used to analyze the contour of the ribosomal mRNA track, yielding information on its "height" as well as its "length" dimension. Examination of several ribosome-binding sites, including those containing very stable secondary structure, indicated that the "height" of the mRNA track is quite roomy, while the nucleotide distance between the site of Shine-Dalgarno annealing, the P site, and the 3'-edge of the mRNA track is fixed. The data suggest a mechanism for tethering regulatory elements to the ribosome during translation.

Base Sequence↗
PubMed1993

Characterization of a duplication in the terminal band of 4p by molecular cytogenetics.

An infant with multiple anomalies including small head, large apparently low-set ears, beaked nose, micrognathia, choanal stenosis, proptosis, atrial-septal defect, and left inguinal hernia was found, on chromosome analysis, to have a longer than normal terminal band 4p16 by G and R-banding. In situ hybridization of biotin-labeled DNA probes C39, BJ14, BJ54, BJ19, BJ7, and BJ11 showed them to be duplicated. Probes I14, A157.1, and the telomeric sequence, (TTAGGG)n, which hybridized to the more distal part of 4p16.3, were not duplicated. These results confirm the impression by G and R-banding of a duplication within band 4p16, a region extending from approximately 2.1 Mb from the telomere, proximally, to the junction of 4p16.1 and 4p15.3. This is the smallest confirmed duplication of distal 4p reported to date, with many of the classical findings of dup(4p) syndrome.

Abnormalities, Multiple↗
PubMed1993

The effect of testing anxiety on blood pressure.

The effect of stress on blood pressure is under debate. Of concern, with the trend toward fitness, is whether anxiety about one's body image may also raise blood pressure. The purpose of this study was to evaluate the effect of testing anxiety on the blood pressure of persons taking a lifestyle and fitness evaluation test. First year nursing students had their blood pressures measured by fitness program technicians as part of a fitness test. Students then had their blood pressures measured by the same technicians in a non-testing situation. Students also completed a social physique anxiety scale to separate those with high and low physique anxiety. Analysis of variance revealed that there was a significant difference in diastolic blood pressure between the evaluative (during the fitness test) and the non-evaluative situations (p = 0.0001). There was no significant difference in blood pressure in those students with high versus low social physique anxiety but those with high anxiety had higher diastolic blood pressures during the non-evaluative situation than did those with low anxiety. These findings indicate that, while the evaluative situation appears to be a more important factor in the evaluation of diastolic blood pressure than anxiety regarding one's physique or body image, there is an interaction effect that should be further examined.

Adolescent↗
PubMed1992

The alpha-subunit of the skeletal muscle sodium channel is encoded proximal to Tk-1 on mouse chromosome 11.

Recent evidence suggests that the human neuromuscular disorders, hyperkalemic periodic paralysis and paramyotonia congenita, are both caused by genetic defects in the alpha-subunit of the adult skeletal muscle sodium channel, which maps near the growth hormone cluster (GH) on Chromosome (Chr) 17q. In view of the extensive homology between this human chromosome and mouse Chr 11, we typed an interspecies backcross to determine whether the murine homolog (Scn4a) of this sodium channel gene mapped within the conserved chromosomal segment. The cytosolic thymidine kinase gene, Tk-1, was also positioned on the genetic map of Chr 11. Both Scn4a and Tk-1 showed clear linkage to mouse Chr 11 loci previously typed in this backcross, yielding the map order: TrJ-(Re, Hox-2, Krt-1)-Scn4a-Tk-1. No mouse mutant that could be considered a model of either hyperkalemic periodic paralysis or paramyotonia congenita has been mapped to the appropriate region of mouse Chr 11. These data incorporate an additional locus into the already considerable degree of homology observed for these human and mouse chromosomes. These data are also consistent with the view that the conserved segment region may extend to the telomere on mouse Chr 11 and on human 17q.

Animals↗
PubMed1992

Linkage, but not gene order, of homologous loci, including alpha-L-iduronidase (Idua), is conserved in the Huntington disease region of the mouse and human genomes.

alpha-L-iduronidase (IDUA), which when deficient causes mucopolysaccharidosis type I, is located near the Huntington disease locus (HD) on human Chromosome (Chr) 4p16.3, approximately 10(6) base pairs (bp) from the telomere. As part of our continuing efforts to define a detailed comparative map for this chromosomal segment in mice and humans, we have used an interspecific backcross between C57BL/6J and an inbred strain derived from Mus spretus to map Idua, the mouse homolog of IDUA. We also mapped the mouse homolog of D4S115, an anonymous locus approximately 250 kb proximal to IDUA. As expected, both Idua and D4S115h are located on the proximal portion of mouse Chr 5 near homologs for other loci on human Chr 4p. Comparison of gene order in mice and humans demonstrates, however, that a chromosomal rearrangement within this conserved synteny has occurred since divergence of lineages leading to mice and humans.

Animals↗
PubMed1992

Radiation hybrid map spanning the Huntington disease gene region of chromosome 4.

Radiation hybrid (RH) mapping was used to construct a map of 11 markers in the distal 4 Mb of the short arm of chromosome 4, the region containing the Huntington disease gene. Two different methods for deriving the order of the markers were compared and both arrived at the same order as being the most likely. This order is also consistent with both the physical map constructed using pulsed-field gel electrophoresis (PFGE) and the meiotic linkage map. Comparing the RH map to the map determined by PFGE provided the means to equate RH map units (centirays) with actual physical distance in kilobases of DNA. In addition, a simple procedure for reducing the complexity of human DNA in radiation hybrids is described. One cell line isolated using this procedure contains, as its only human DNA, approximately 2 Mb surrounding the Huntington disease gene.

Chromosome Mapping↗
PubMed1991

VH gene analysis of spontaneously activated B cells in adult MRL-lpr/lpr mice. J558 bias is not limited to classic lupus autoantibodies.

To determine the genetic origins of lupus auto-antibodies, we analyzed the relationship between VH gene usage and auto-Ag-binding properties of 352 B cell hybridomas derived from MRL-lpr/lpr mice. The hybridomas were derived from neonatal, 1-month-old, 3-month-old, and 6-month-old mice. The experimental strategy provided that the hybridomas were monoclonal at initial evaluation, so the Ag binding and V gene frequencies of the entire population could be determined. Initially, 1032 Ig-producing hybridomas were evaluated for binding to six Ag; VH gene family use was determined in 119 anti-DNA and anti-rabbit thymus extract (RTE) antibodies (autoantibodies) and in 233 age-matched Ig that did not bind to any of the six Ag (nonbinders). Neonatal B cells, including cross-reactive IgM autoantibodies and nonbinder IgM, used relatively 3' VH genes. The majority of B cells in adult mice used VH genes of the J558 family. Although J558 use was significantly higher among the autoantibodies (anti-DNA and anti-RTE) than among the nonbinder Ig, this difference was due to a higher frequency of J558 use by 1-month-old mice. At 3 months, J558 use by the nonbinder Ig increased to the same frequency of J558 use as in the autoantibody population. J558 use in both groups of antibodies exceeded a previously reported estimation of J558 expression in the functional B cell repertoire of young adult MRL-lpr/lpr mice. Several subgroups of antibodies that share properties with pathogenic Ig, including IgG, cross-reactive Ig, and anti-dsDNA autoantibodies, demonstrated a marked preferential expression of the J558 family. These results suggest that there is an age-related bias in the activation of B cells using J558 VH genes in MRL-lpr/lpr mice that is under the influence of a selective force distinct from, or in addition to, an ssDNA or RTE auto-Ag-driven response.

Animals↗
PubMed1991

Effects of treadmill exercise on weight cycling in female mice.

Weight cycling increases food efficiency and rate of weight regain. This study induced weight loss in adult female B6D2F1 mice via dietary energy restriction and exercise to determine whether the weight loss regimen influenced rate of weight regain. Four groups of animals were studied: RES, restricted (food restricted); EX, exercised (treadmill exercised); SC, sham control (treadmill exposure, not exercised); LC, lab chow control (appropriately aged control). Both EX and SC voluntarily reduced food intake to the level of the RES animals. The RES group showed increased food efficiency and rate of weight regain relative to the LC group; this effect was attenuated in both the EX and SC groups. These findings demonstrate that a) the cycling phenomenon occurs in mice, and b) stressors such as forced exercise or exposure to a novel environment can modify the pattern of food efficiency and rate of weight regain engendered by dietary restriction.

Animals↗
PubMed1990

Hyperkalaemia during massive blood transfusion in paediatric craniofacial surgery.

Children undergoing major craniofacial surgery (MCFS) often require transfusion in excess of one blood volume. Therefore they were the subject of a retrospective review which looked at the longitudinal trend of plasma potassium concentration [K+] during surgery. Ten of eleven children had a statistically significant increase in plasma potassium concentration during their intraoperative course and in five the potassium concentration exceeded 5.5 mmol.L-1. This was in contrast to the stable intraoperative plasma [K+] observed in a control group which did not receive blood transfusion. All MCFS children received a blood transfusion with red blood cell concentrates (RBCconc). The age of the units of RBCconc which had been transfused was 16.1 +/- 8.4 days. The amount of extracellular potassium in 28 units of RBCconc was determined in order to estimate the amount of free potassium (Kdose) which the MCFS group received. The plasma [K+] in units of RBCconc less than 1 week of age was less than 20 mmol.L-1, whereas in units aged greater than 2 weeks it was greater than 40 mmol.L-1. The estimated Kdose was 0.2-1.6 mmol.kg-1. We concluded that the amount of extracellular potassium in units of RBCconc was clinically important and may give rise to hyperkalaemia during massive blood transfusion.

Blood Transfusion↗
PubMed1990

Physical maps of 4p16.3, the area expected to contain the Huntington disease mutation.

The gene for Huntington disease, a neurodegenerative disorder with autosomal dominant inheritance, has been localized to the terminal portion of the short arm of human chromosome 4 (4p16.3) by linkage analysis. Since eventual isolation of the gene requires the application of high-resolution genetic analysis coupled with long-range DNA mapping and cloning techniques, we have constructed a physical map of the chromosomal region 4p16.3 using more than 20 independently derived probes. We have grouped these markers into three clusters which have been ordered and oriented by genetic and somatic cell genetic mapping information. The mapped region extends from D4S10 (G8) toward the telomere and covers minimally 5 Mb.

Chromosome Mapping↗
PubMed1990

Comparison of four methods for rapid detection of Pneumocystis carinii in respiratory specimens.

Four stains for the detection of Pneumocystis carinii in respiratory specimens were compared for sensitivity, specificity, preparation time, and ease of interpretation. One hundred specimens were collected. Of these, 50 were induced sputum specimens and 50 were bronchoalveolar lavage fluid. All specimens were stained with Diff-Quik (DQ) (a modified Giemsa stain), a quick silver stain, and direct and indirect immunofluorescence stains. A positive specimen was defined as any smear positive by two or more of the methods. Fifty-eight percent of specimens were positive. Seventy-four percent of the sputum specimens and 42% of the bronchoalveolar lavages were positive. The sensitivities for detection of P. carinii in sputum were 92% with silver stain, 97% with direct immunofluorescence assay (DFA), 97% with indirect immunofluorescence assay (IFA), and 92% with DQ. The sensitivities for detection in bronchoalveolar lavage were 86% with silver stain, 90% with DFA, 86% with IFA, and 81% with DQ. Preparation times varied from 90 min for the silver stain and IFA to 3 min for DQ. Costs of the tests varied from $1.50 per slide for DQ to $10.00 per slide for the silver stain and DFA. Reading times varied from 10 to 30 min for the silver stain and DQ to less than 5 min for the immunofluorescence assays. We conclude that all of these tests are viable options for the clinical laboratory, and the choice will be influenced by factors such as clinical volume, ability to batch specimens, and expertise of technological support. A reasonable option may be to use the quick and inexpensive DQ as a screening test and to confirm negative smears with a more sensitive assay.

Bacteriological Techniques↗
PubMed1989

A new DNA marker (D4S90) is located terminally on the short arm of chromosome 4, close to the Huntington disease gene.

Genetic linkage studies have mapped Huntington's disease (HD) to the distal portion of the short arm of chromosome 4 (4p16.3), 4 cM distal to D4S10 (G8). To date, no definite flanking marker has been identified. A new DNA marker, D4S90 (D5); which maps to the distal region of 4p16.3, is described. The marker was used in a genetic linkage study in the CEPH reference families with seven other markers at 4p16. The study, together with knowledge of the physical map of the region, places D4S90 as the most distal marker, 6 cM from D4S10. A provisional linkage study with HD gave a maximum lod score of 2.14 at a theta of 0.00 and no evidence of linkage disequilibrium. As D4S90 appears to be located terminally, it should play an important role in the accurate mapping and cloning of the HD gene.

Blotting, Southern↗
PubMed1989

An evaluation of the Kodak Ektachem clinical chemistry slide for theophylline.

We evaluated the Kodak Ektachem clinical chemistry slide for assay of theophylline. Assay precision and accuracy were acceptable in the therapeutic range although precision was poor at low levels of theophylline. The assay performed well with patients' samples using the Abbott TDx as the reference procedure but, as indicated by the manufacturer, uremic samples gave a positive bias, particularly in the therapeutic range. Finally, the significant bias observed with Quality Control material, probably due to matrix sensitivity, is a possible drawback.

Humans↗
PubMed1989

Vogt-Koyanagi-Harada syndrome--isolation of cloned T cells with specificity for melanocytes and melanoma cells.

The pathogenesis of Vogt-Koyanagi-Harada syndrome is poorly understood. A unifying mechanism for its diverse clinical manifestations affecting central nervous system, eye, integument and auditory system has not been found, although many authors have suggested that the features of the disease are the result of autoimmune responses. We performed immunological studies on two patients with Vogt-Koyanagi-Harada syndrome. In one case antibodies to melanoma cells in cytotoxic assay were detected, which it was thought may indicate the presence of antibodies to melanocytes. In the second patient three clones of interleukin-2-dependent T cells were isolated which appeared to have specificity in both cytotoxic and proliferative assays to cultured normal melanocytes and to three allogeneic melanoma cells. These findings further support a role for autoimmunity to pigmented cells in the pathogenesis of Vogt-Koyanagi-Harada syndrome. However, the precise role of autoimmunity in this disease is yet to be established.

Adolescent↗