Transmission of hepatitis C virus: rates, routes, and cofactors.
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Disease Transmission, Infectious↗
Biomedical subjects
M MacDonald
Publications and source records attributed to M MacDonald.
HIV testing at a gay men's clinic, Melbourne.
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Acquired Immunodeficiency Syndrome↗
Do excretory-secretory products of Onchocerca gibsoni contain phosphorylcholine attached to O-type glycans?
Excretory-secretory products (ES) of adult male Onchocerca gibsoni contain phosphorylcholine (PC). PC-ES are detected as a smear of M(r) approximately 60- approximately 200 kDa by western blotting employing a monoclonal antibody (mAb) against PC, suggesting that they are glycoproteins. Exposure of PC-ES to N-glycosidase F results in weak and inconsistent loss of binding of the mAb, indicating that unlike the situation with respect to ES of Acanthocheilonema viteae, PC is highly unlikely to be solely attached to N-type glycans. Conversely, treatment of O. gibsoni PC-ES with mild alkali, a strategy for removing O-type glycans, abolishes mAb binding. These results suggest that PC may be attached to O. gibsoni proteins mainly via O-type glycans, and raise the possibility that filarial parasites may vary with respect to their mode of attachment of PC. The implications of this with respect to the design of inhibitors of PC attachment for use as anti-filarial drugs, are discussed.
Amidohydrolases↗
An improved approach to prepare human brains for research.
We describe two protocols for preparing human brains collected for research and diagnosis. In both protocols, one half brain is processed for research and the other for neuropathological evaluation. Clinical, neuropathological and tissue mRNA retention data are used for sample categorization. In protocol 1, coronal, whole hemisphere slices cut at standardized landmarks are frozen with a cooling device at -90 degrees C, which yields discrete anatomical structures. In selected instances, small blocks of brain are frozen at -160 degrees C in liquid nitrogen vapor. Cooling device or liquid nitrogen vapor frozen samples are suitable for in situ hybridization, protein blotting or immunohistochemistry. Morphological freezing artifacts are minimal. In protocol 2, one half brain is frozen en bloc on dry ice; this tissue is suitable for regional evaluation of gene expression or neurochemistry. Morphological freezing artifacts are severe. In both protocols, the other half brain is fixed in formalin prior to sectioning and diagnostic evaluation. The standardized selection of paraffin blocks from each brain allows precise diagnoses to be established, including identification of dangerous infectious processes; moreover, it makes it possible to produce a set of uniformly selected blocks and slides for comparative studies. These protocols lead to standardized tissue preparation for research and reduce variables impairing interpretation and comparison of data.
Brain↗
Mapping of a human A2a adenosine receptor (ADORA2) to chromosome 22.
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Animals↗
Mutation analysis for cystic fibrosis to determine carrier status in 167 sperm donors from the Nebraska Genetic Semen Bank.
Cystic fibrosis is the most common autosomal recessive disorder in Caucasian populations, with an approximate frequency of 1/2500 live births and a carrier frequency of 1/25. Due to the high rate of predicted carriers (> 63,000) in the Nebraska population (1990 U.S. Census = 1,578,358), we analyzed sperm DNA obtained from semen donors at the University of Nebraska Genetic Semen Bank for eight of the more common mutations to determine the frequency and diversity in our population. The subjects included 167 semen donors (31 normal healthy donors, 56 infertility patients, 21 prevasectomy patients, and 59 prechemotherapy or preradiation cancer patients). The mutations analyzed included delta F508, R117H, G542X, S549R/N, G551D, R553X, R560T, and W1282X. Analyses were performed using PCR amplified products that were analyzed using polyacrylamide gel electrophoresis, slot blot, and restriction endonuclease digestion. These results were correlated with results from the clinical semen analyses and selected clinical parameters. Results for the total donor population studied showed that the delta F508 mutation was present in 8/167 (4.8%) donors, the R117H mutation was present in 4/167 (2.4%) donors and the G542X mutation was present in 1/167 (0.6%) donors. The observed number of carriers from this population, 13/167 (7.8%), was significantly greater (P = 0.02) than that expected assuming a carrier frequency of 1/25. The excess of carriers was restricted to the subgroup of infertility patients. This suggests that CF carriers may be at higher risk for infertility than the general population.
Cystic Fibrosis↗
High resolution localization of recombination hot spots using sperm typing.
We have applied sperm DNA typing to determine the distribution of crossover events within a one megabase region of the short arm of human chromosome 4 near the locus for Huntington disease. A total of 29 recombinants were detected among 602 sperm typed after whole genome amplification. These recombinants were typed for seven polymorphic markers. The 280 kilobase D4S10-D4S126 interval was found to undergo recombination at a 6-9-fold greater rate per unit of physical distance than the adjacent 720 kb D4S126-D4S127 interval. Sperm typing has the potential to dissect mammalian recombination hot spots to the point where DNA sequence analysis may reveal the molecular basis for hyperrecombination.
Base Sequence↗
Some preliminary data on the nature/structure of the PC-glycan of the major excretory-secretory product of Acanthocheilonema viteae (ES-62).
The structure of the PC-glycan of the major excretory-secretory product (ES-62) of Acanthocheilonema viteae has been investigated using endoglycosidases and lectins. Results obtained raise the possibility that it may be of the high mannose type. This, and the insensitivity of the PC-glycan to treatments which remove PC or choline from bacterial PC-glycans, suggests that it may be more analogous to fungal, than to bacterial PC-containing glycans.
Animals↗
The origin of 47,XXY and 47,XXX aneuploidy: heterogeneous mechanisms and role of aberrant recombination.
We investigated the parent and cell division of origin of the additional sex chromosome in 142 males with a 47,XXY constitution and 50 females with a 47,XXX constitution. In 66 of the 47,XXY males the additional chromosome was paternal in origin and in 76 it was maternal in origin, while among the 47,XXX females only 5 had an additional paternal X chromosome, the remaining 45 having an additional maternal chromosome. Among the 107 maternally derived aneuploids for whom it was possible to determine the cell division of origin, 73 were the result of a mat MI error, 24 the result of a mat MII error and 10 the result of a post zygotic mitotic (PZM) error involving the maternal X chromosome. Among those in which the non-disjunction was attributable to an error at the first meiotic division (MI) we observed three different mechanisms of origin. Approximately 30% were associated with complete absence of recombination (nullichiasmate); approximately 24% were associated with a normal number of recombinant events but an abnormal distribution of exchanges (perturbed recombination), while approximately 45% were associated with a normal number and distribution of recombinant events (normochiasmate). Nondisjunction due to an error at the second meiotic division (MII) was associated with a slight reduction in the total number of recombinant events and an abnormal distribution of exchanges. Thus of the four different meiotic mechanisms of origin, three were associated with an abnormal number and/or distribution of exchange events. There was no evidence of an increased paternal age in the aneuploids of paternal origin.(ABSTRACT TRUNCATED AT 250 WORDS)
Aneuploidy↗
Trinucleotide repeat length and progression of illness in Huntington's disease.
The genetic defect causing Huntington's disease (HD) has been identified as an unstable expansion of a trinucleotide (CAG) repeat sequence within the coding region of the IT15 gene on chromosome 4. In 50 patients with manifest HD who were evaluated prospectively and uniformly, we examined the relationship between the extent of the DNA expansion and the rate of illness progression. Although the length of CAG repeats showed a strong inverse correlation with the age at onset of HD, there was no such relationship between the number of CAG repeats and the rate of clinical decline. These findings suggest that the CAG repeat length may influence or trigger the onset of HD, but other genetic, neurobiological, or environmental factors contribute to the progression of illness and the underlying pace of neuronal degeneration.
Adolescent↗
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↗
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↗
Laboratory request forms.
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Family Practice↗
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↗
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↗
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↗
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↗
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↗