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Biomedical subjects

A Mackenzie

Publications and source records attributed to A Mackenzie.

At least 73 records · Page 4Linked to original sources

Nucleotide sequence comparisons of turnip yellow mosaic virus isolates from Australia and Europe.

The genomic sequences of four isolates of turnip yellow mosaic virus (TYMV-Cd) from Australia, and three TYMV-1 (type) and three TYMV-2 (cauliflower) isolates from Europe were compared by cDNA-RNA hybridization tests, by analysis of the fragments produced from cDNA-RNA hybrids by restriction endonuclease treatment, and by determining the 3' terminal nucleotide sequences of their coat protein mRNAs. All three methods showed only slight differences (ca. 1%) between the mRNA sequences of different TYMV-1 and TYMV-Cd isolates, and did not distinguish between those groups of isolates. By contrast, the nucleotide sequences of TYMV-2 isolates differed from those of the other TYMVs by ca. 5% (sequence analysis) to 11% (restriction fragment analysis). Published biogeographic evidence has indicated that the TYMV-Cd and TYMV-1 populations probably separated more than 12,000 years ago. This implies that these TYMV genomes have changed at a rate of, at most, 1% in 10,000 years.

Australia↗

The classification of tymoviruses by cDNA-RNA hybridization and other measures of relatedness.

The relationships of twelve tymoviruses have been assessed by cDNA-RNA hybridization. In addition, the percentage molar nucleotide composition of the genome of the PD strain of Kennedya yellow mosaic virus and the percentage molar amino acid composition of the coat proteins of cacao yellow mosaic, Kennedya yellow mosaic and turnip yellow mosaic (Cardamine strain) viruses were estimated. These as well as published serological comparisons and genome and coat protein composition determinations were used to compute classifications of tymoviruses using various "metrics", and simple numerical methods were used to compare the classifications. Measures of relatedness estimated from cDNA-RNA hybridization and base ratio data correlated significantly with each other, but were less closely correlated with those calculated from amino acid data, and did not correlate with those calculated from serological tests. The serological relationships correlated significantly with estimates of relatedness calculated from amino acid data, but not with those based on hybridization or base ratio data. The differences between these classifications mostly resulted from the anomalous behaviour of eggplant mosaic virus, its particles are serologically close to those of other tymoviruses that naturally infect species of the tobacco family, whereas in cDNA-RNA hybridization tests eggplant mosaic virus is closest to the tymoviruses that infect legumes. Similar but smaller anomalies in the characteristics of other tymoviruses were also found.

Amino Acids↗

The characteristics of alcoholics frequently lost to follow-up.

In a follow-up of 85 alcoholic men, 93% were interviewed or confirmed deceased 8 years after discharge from hospital. The sample was also followed up at 1 and 3 years postdischarge. Follow-up rates of other published studies are discussed. Scales to assess difficulty of interview and difficulty of location were developed. Factor analysis revealed the differential characteristics of subjects defined as difficult to locate, difficult to interview or missing. Subjects who are difficult to locate, or who in the extreme case will go missing, tended to have poorer social functioning prior to intake and to be residentially unstable during the follow-up period, characteristics that tend to correlate with worse drinking outcome. Subjects who are unwilling to be interviewed tended to be residentially stable and show better interpersonal adjustment at follow-up. Less intensive location procedures would have resulted in data loss from those classified as difficult to locate. Less persuasive interview techniques would have resulted in data loss from those classified as difficult to interview. Early termination of the follow-up would also have resulted in data loss from the latter group. The distinct types of data biases that would be introduced by loss of information from each of the above subgroups are examined.

Adult↗

Persistence of virulent Semliki Forest virus in mouse brain following co-inoculation with defective interfering particles.

Semliki Forest virus (SFV) normally causes an acute lethal encephalitis in mice following intranasal inoculation. However, animals co-administered with 10 LD50 SFV and defective interfering (DI) SFV survive the infection without clinical signs of disease. In this report we demonstrate the isolation of infectious virus from the brains of 12/169 protected mice up to 6.5 months post-infection. Although, with one exception, mice were clinically normal, five of 12 of the SFV isolates were identical to the original virus as judged by plaque morphology, maximum temperature for growth, virulence in mice and pathology. Others were less virulent (although not any were plaque or temperature-sensitive mutants) and on re-inoculation into fresh mice caused a demyelinating pathology which was not an attribute of the original inoculum. How the virulent virus can persist in brain, sometimes in amounts in excess of 100 LD50, without causing disease remains to be determined.

Animals↗

Partial purification of an osteolytic toxin from Pasteurella multocida.

A protein toxin apparently composed of one polypeptide with an estimated Mr of 155,000 was purified from sonicated cells of a type D strain of Pasteurella multocida (LFB3) by preparative polyacrylamide gel electrophoresis (PAGE) and DEAE-Sephadex A50 chromatography. Its specific activity was 150-fold greater than that of the crude extract. The partially purified protein was cytotoxic for embryonic bovine lung cells, lethal for mice and caused turbinate atrophy in gnotobiotic pigs; a single intraperitoneal injection of approximately 360 ng kg-1 caused 50% turbinate atrophy. Reversal of the two-step purification procedure using DEAE-Sephacel chromatography followed by preparative PAGE increased the yield of toxin 30-fold; the specific activity of the partially purified toxin was 1970-fold greater than that of the crude extract.

Bacterial Toxins↗

Mortality and illness in male alcoholics: an 8-year follow-up.

An 8-year follow-up was conducted on a group of male alcoholics. Their mortality and illness records were examined. The number of observed deaths is 4.7 times that expected. The excess deaths appear to be due to causes frequently associated with alcoholism. Patient characteristics predictive of mortality are presented. Inpatient stays in general hospitals, for reasons other than alcoholism, totaled almost four times the duration expected. The relationships between drinking patterns and hospitalizations are studied. Clinical tests, which show improvement in response to abstinence, are suggested as positive reinforcers for patients in alcoholism treatment.

Adult↗

Absorption of chloramphenicol sodium succinate after intramuscular administration in children.

Because it is thought that chloramphenicol is poorly absorbed after intramuscular administration, we compared blood levels of chloramphenicol after intramuscular administration with those after intravenous administration in children with a variety of diagnoses. Fifty-seven children were studied on 62 occasions while they were receiving chloramphenicol sodium succinate (25 mg of chloramphenicol per kilogram of body weight) intramuscularly every six hours. The peak level of chloramphenicol was 19.5 +/- 5.99 micrograms per milliliter (mean +/- S.D.) in 11 children after the first dose and 31.4 +/- 12.99 micrograms per milliliter in 51 children after two or more doses. The lowest peak level after intramuscular administration was 13 micrograms per milliliter, which is in the therapeutic range of 10 to 30 micrograms per milliliter. Thirteen children were studied on 17 occasions while they were receiving chloramphenicol sodium succinate (25 mg of chloramphenicol per kilogram) intravenously every six hours. The peak level of chloramphenicol was 19.4 +/- 6.37 micrograms per milliliter in eight children after the first dose and 28.2 +/- 11.09 micrograms per milliliter in nine children after two or more doses. The area under the serum level curve was not significantly different after intramuscular and intravenous administration. We conclude that chloramphenicol sodium succinate is well absorbed after intramuscular administration. This route is cheaper, it demands less staff time, and it does not carry the risks of sepsis and overhydration associated with intravenous therapy.

Absorption↗

Intraneuronal enzymic inclusions in the histological diagnosis of scrapie.

Cumulative results are presented of histopathological and enzyme histochemical findings in sheep naturally or experimentally infected with scrapie compared with healthy controls or animals with other diseases. Two hundred and sixty-eight sheep were examined, including 210 cases of clinical or suspected scrapie. According to the nature and distribution of histopathological changes, especially neuropil vacuolation and neuronal vacuoles, scrapie-affected sheep were classified into groups. In particular, examination of medulla oblongata revealed a consistently different pattern of lesions between natural scrapie (type A) and experimental scrapie (type B). Cytoplasmic enzymic inclusions demonstrated by methods for beta-glucuronidase and for acid phosphatase were regularly found in neurones from scrapie sheep but not from control animals. They appeared to be more prevalent in type B than in type A scrapie and were demonstrable even in tissue affected by post-mortem autolysis. The distribution of enzymic inclusions ranged from Betz cells of cerebral cortex to grey matter of the lumbar region of spinal cord. The detection of enzymic inclusions is a useful diagnostic criterion and has been incorporated into histological diagnostic procedures for scrapie.

Acid Phosphatase↗

Protection of mice infected with a lethal dose of Semliki Forest virus by defective interfering virus: modulation of virus multiplication.

Certain defective interfering (DI) Semliki Forest virus (SFV) preparations completely protected the majority of mice inoculated with a normally lethal dose of SFV, and the surviving mice showed no signs of disease during the period of observation. Depending upon which DI SFV preparation was used, the survivors were resistant to challenge with 100 LD50 SFV (DI SFV p13a), or were completely sensitive (DI SFV p4), the latter having evidently failed to establish a protective immunity. In this report we compared the ability of these two DI SFV preparations to inhibit multiplication of infectious virus in mice inoculated with 10 LD50 SFV. The following conclusions emerged: virus multiplication was profoundly inhibited in the majority of mice treated with either of the DI virus preparations although there was significant multiplication in most tissues, including brain. The number of mice showing evidence of reduced infectivity titres (58%) correlated well with the 60% which survived without disease in lethality experiments. Despite the presence of infectivity, no SFV antigen or histopathological lesions were detected in brain or spinal cord. The DI virus preparations p4 and p13a altered the distribution of infectivity in the mouse in different ways: during the first 2 days of the infection modulated by DI virus p4, the infectivity titres (in brain, olfactory lobes and spleen) were comparatively high, being greater than 1% of those in mice inoculated with standard virus alone. However, from day 3, titres declined precipitously and there was little infectivity in any of the tissues investigated. On the other hand, mice treated with DI SFV p13a had, over the entire duration of infection, greatly reduced though significant infectivity in brain, olfactory lobes and spleen and very little infectivity in serum. In a minority of mice (14.5%), DI virus p13a altered the distribution of infectivity between different tissues so that there was significantly decreased virus in just one or two of the four tissues investigated, suggesting that the infection was being subtly modulated by the DI virus. Interference assays failed to detect DI SFV in any tissue samples although the effects of DI virus on infection in the mouse were obvious.

Animals↗

Feasibility of discharge of chronic psychiatric patients.

In a survey of all (2795) chronic psychiatric patients resident in Victorian Mental Health Division hospitals, charge nurses were asked to assess patients' levels of physical and psychological dependence on nursing care, aggressive and difficult behaviour and their preferred future placement. The vast majority were 'old' chronic patients and nurses considered the present placement as the most appropriate for two-thirds of the surveyed population. We adopted our own criteria of placement needs, such as level of physical and psychological dependence, behavioural problems and treatment received. Of the 2795 patients, one-quarter (682) would require continuing hospital care. The remainder could be transferred, depending on their characteristics, to intensive or general nursing care homes, hostels or special accommodation houses, provided that such facilities are available and the participation of patients in various therapeutic activities was ensured.

Adult↗

Immunohistochemical demonstration of glial fibrillary acidic protein in scrapie.

Although little is known about its metabolism, glial fibrillary acidic (GFA) protein has become widely used as a cell-specific, species-non-specific antigenic marker for normal or pathologically altered astroglia. So far there have been few investigations on GFA protein in relation to scrapie and analogous spongiform encephalopathies although there has been a need for an unequivocal method for the discrimination of different types of glia in these diseases. In the present studies, a commercially available antiserum to GFA protein incorporated in a peroxidase-antiperoxidase procedure was applied to paraffin sections of brain and spinal cord from mice affected with scrapie, avirulent Semliki forest virus and cuprizone encephalopathy, and to tissues from healthy and scrapie-affected sheep. Excellent delineation of GFA protein was obtained in astroglial cell bodies and processes and in fibrils in the glia limitans and in perivascular and subependymal sites. The method was extremely sensitive and selective. A massive increase in GFA protein in scrapie-affected mice paralleled an increase in reactive astrocytes and facilitated the construction of astroglial lesion profiles for scrapie and the other encephalopathies. In sheep, abundant GFA protein occurred in both healthy and in scrapie-affected animals and in the tissues examined the differences were not conclusive.

Animals↗

Cloning in a cosmid vector of complete 37 kb and 25 kb ribosomal DNA repeat units from the chicken.

DNA fragments of up to 40 kb containing rRNA-coding sequences have been isolated from a chicken liver DNA library prepared in the cosmid pHC79. Characterization of the cloned DNA by R-loop and restriction mapping has shown that there are two size classes of repeat unit, one of 37 kb and one of 25 kb, the larger of which is a family of units which vary slightly in size. These two classes were shown to be present in the DNA of a single chicken. The size of the internal transcribed spacer in the chicken was measured to be 4.4 kb from analysis of R-loops and heteroduplexes between chicken and Xenopus laevis rDNAs. No introns were observed in either the 18 S or the 28 S coding sequences. The number of copies of the chicken rDNA unit was measured by titration against the cloned sequences to be 202 +/- 51 per haploid genome.

Animals↗

The effect of defective-interfering Semliki Forest virus on the histopathology of infection with virulent Semliki Forest virus in mice.

The majority of mice inoculated with a mixture of a lethal dose of virulent Semliki Forest virus (SFV) strain ts+ and defective-interfering (DI) SFV remained completely health, with virus infectivity levels in brain tissue reduced by 99.9%. The results of previous studies had suggested that these effects were primarily the result of the intrinsic interfering capacity of DI virus rather than of host defense responses. Because SFV strain ts+ and an avirulent strain of SFV have clearly distinguishable histopathologic effects in brain tissue, the capability of DI virus to change the virulent into the avirulent form of the disease was examined. Modulation of strain ts+ virus infection by DI virus was accompanied by a complete absence of histopathologic changes despite significant levels of infectious virus and thus differed qualitatively from infection with avirulent SFV. These results provide further evidence that the interference is not mediated through stimulation of an immune cell infiltration.

Animals↗