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Biomedical subjects

A M Johnson

Publications and source records attributed to A M Johnson.

At least 163 records · Page 9Linked to original sources
PubMed1995

Phylogenetic relationships between Toxoplasma and Sarcocystis deduced from a comparison of 18S rDNA sequences.

The current taxonomy of parasites in the genus Sarcocystis is largely based on morphological characteristics as well as on host specificity and life-cycle structure. Recently, phylogenetic analyses of partial ribosomal RNA (rRNA) sequences provided support for paraphyly of Sarcocystis. We have tested the validity of this hypothesis by sequencing the complete 18S rRNA genes of Sarcocystis arieticanis, Sarcocystis gigantea and Sarcocystis tenella and comparing them with gene sequences derived from other taxa of the phylum Apicomplexa. The results obtained from this study do not reject the hypothesis of monophyly of Sarcocystis species, although the bootstrap data were inconclusive for some species.

Animals↗
PubMed1995

Heat shock proteins of Toxoplasma gondii.

We have investigated heat shock protein (HSP) expression in mouse-virulent and -avirulent strains of Toxoplasma gondii by performing Western blot analysis using a monoclonal antibody against HSP65 of Mycobacterium bovis and a polyclonal antiserum against HSP70 of Plasmodium falciparum as primary antibodies. We initially observed that murine macrophages express HSP65 when infected with either virulent or avirulent strains, a result which contradicts previous reports. Differential HSP expression consistent which virulence was observed between strains, with high levels of a 70kDa HSP (HSP70) only detected in virulent strains in vivo. This protein was not observed in virulent strains in the immunocompromised mouse or in vitro, suggesting induction by immunological stress. This protein was only poorly expressed in avirulent strains. A 65kDa protein was observed in all strains in vivo and in vitro, suggesting a shared epitope with HSP70. These results are consistent with the hypothesis that the induced expression of HSP70 in virulent strains of T. gondii by immunological stresses may provide protection for these strains against cell damage associated with invasion of the host, allowing the virulent strains to persist as tachyzoites without the requirement for the encystation observed in avirulent strains.

Animals↗
PubMed1995

Inhibition of chloroplast DNA recombination and repair by dominant negative mutants of Escherichia coli RecA.

The occurrence of homologous DNA recombination in chloroplasts is well documented, but little is known about the molecular mechanisms involved or their biological significance. The endosymbiotic origin of plastids and the recent finding of an Arabidopsis nuclear gene, encoding a chloroplast-localized protein homologous to Escherichia coli RecA, suggest that the plastid recombination system is related to its eubacterial counterpart. Therefore, we examined whether dominant negative mutants of the E. coli RecA protein can interfere with the activity of their putative homolog in the chloroplast of the unicellular green alga Chlamydomonas reinhardtii. Transformants expressing these mutant RecA proteins showed reduced survival rates when exposed to DNA-damaging agents, deficient repair of chloroplast DNA, and diminished plastid DNA recombination. These results strongly support the existence of a RecA-mediated recombination system in chloroplasts. We also found that the wild-type E. coli RecA protein enhances the frequency of plastid DNA recombination over 15-fold, although it has no effect on DNA repair or cell survival. Thus, chloroplast DNA recombination appears to be limited by the availability of enzymes involved in strand exchange rather than by the level of initiating DNA substrates. Our observations suggest that a primary biological role of the recombination system in plastids is in the repair of their DNA, most likely needed to cope with damage due to photooxidation and other environmental stresses. This hypothesis could explain the evolutionary conservation of DNA recombination in chloroplasts despite the predominantly uniparental inheritance of their genomes.

Base Sequence↗
PubMed1995

Risk behaviour and STD acquisition in genitourinary clinic attenders who have travelled.

OBJECTIVE: To investigate the travel history of clients presenting at a genitourinary medicine (GUM) clinic in order to assess the contribution made by sexual partnerships abroad to STD transmission in the UK. SUBJECTS: 386 old and new clients who attended during a 3-month period and who had travelled abroad in the 3 months preceding their visit. METHODS: All participating clients self-completed a confidential questionnaire, the results of which were then linked to their clinical diagnosis (if any). RESULTS: 25% of participants reported a new sexual partner during their most recent trip abroad. In comparison to those not reporting a new partner, they were more likely to be male, travelling alone, to have visited the clinic previously and to have no regular sexual partner. Two-thirds reported never or inconsistently using condoms with these new partners. A total of 11.6% of the STDs diagnosed in the study participants may have been acquired abroad. CONCLUSION: We have found a high rate of new sexual relationships reported by attendees at our GUM clinic, and a low rate of reported condom use. With high HIV incidence rates in many tourist regions, the need for further studies to establish the true extent of imported STDs in the UK is a priority, and primary prevention campaigns to inform travellers are of paramount importance.

Adult↗
PubMed1995

Cardiovascular abnormalities in children with autosomal dominant polycystic kidney disease.

It is known that adults with autosomal dominant polycystic kidney disease (ADPKD) have an increased incidence of cardiovascular abnormalities, including mitral valve prolapse. The cardiac manifestations of ADPKD in the pediatric population have not been well established. To determine the cardiac manifestations of children with ADPKD, echocardiography was performed in 154 children of 66 families in which one parent has ADPKD. Eighty-six affected children and 68 unaffected children were evaluated in a prospective, single-blinded manner by echocardiography. Affected children were defined as those with any cysts on a concurrent renal ultrasound or those predicted to be gene carriers by gene linkage analysis. A 12% incidence of mitral valve prolapse was found in the affected children compared with only 3% of the unaffected children (P < 0.05). ADPKD children, but not their unaffected siblings, demonstrate a significant correlation between left ventricular mass index and systolic blood pressure. Moreover, hypertensive ADPKD children have significantly larger left ventricular mass index than do normotensive ADPKD children. A 3.5% incidence of congenital heart disease was found in the affected group, whereas 2.9% of the unaffected children had congenital heart disease. It was concluded that systemic manifestations of ADPKD, particularly cardiovascular abnormalities, are present even in childhood and these warrant the clinician's attention.

Abnormalities, Multiple↗
PubMed1995

Causes of death in autosomal dominant polycystic kidney disease.

To determine the causes of death in autosomal dominant polycystic kidney disease (ADPKD) patients and to examine whether the extrarenal manifestations of ADPKD influence the causes of death, the medical records of 129 patients who died between 1956 and 1993 were reviewed; 58% of the 129 patients had an autopsy performed. Seventy-seven percent died after reaching ESRD. The mean age at death increased from 51 yr for those who died before 1975 to 59 yr for those who died after 1975, reflecting the introduction of renal replacement therapies. The most common cause of death before 1975 was infection (30%), followed by uremia (28%) and cardiac disease (21%); after 1975, these were cardiac disease (36%) and infection (24%). Infection was equally prevalent before and after 1975, presenting as sepsis in 94% and directly relating to ADPKD in 47% of these patients. Underlying factors for cardiac death were cardiac hypertrophy, seen in 89% of all autopsied patients, and coronary artery disease, seen in 81%. A neurologic event was the cause of death in 12% of patients; these were ruptured intracranial aneurysm in 6%, hypertensive intracranial hemorrhage in 5%, and ischemic stroke in 1%. The mean age of those who died of ruptured intracranial aneurysm was 37 yr. No patient died of renal cancer. Liver cysts were the most common extrarenal manifestation, seen in 70% of the autopsied cases; cysts in other organs were very rare. Colonic diverticula were found in 21%. Thus, the renal and extrarenal manifestations of ADPKD are important contributors to morbidity and mortality.

Autopsy↗
PubMed1995

Sexual behaviour and HIV epidemiology: comparative analysis in France and Britain. The ACSF Group.

OBJECTIVE: France and Britain have similar size populations, yet the incidence of AIDS is threefold higher in France. The objective of this study was to compare data from two surveys recently performed in the two countries, in order to determine whether differences in sexual and drug-use behaviour could explain the different epidemiological patterns. DESIGN: Cross-sectional random sample surveys of France and Britain. RESPONDENTS: In France, 20,055 persons aged 18-69 years and in Britain, 18,876 persons aged 16-59 years were interviewed in 1990-1991. The following indicators were compared in the respondents aged 18-59 years: prevalence of homosexual experience and injecting drug use, number of sexual partners, prevalence of sexual practices, condom use and sex with prostitutes, age of sexual partners. RESULTS: Very similar results were found for the prevalence of male homosexual partnerships. Slightly higher numbers of lifetime partners were reported by French than British men, but no difference was found for recent periods. Anal intercourse and sex with prostitutes was more frequent among heterosexual French people than British people. Condom use was more systematic in Britain than in France. CONCLUSION: Only small differences were found between the two countries, although prevalence of risk indicators were higher in France. These differences combined with early development of prevention policies in Britain, together with the timing of virus introduction, may contribute to differences between the epidemics in the two countries.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Reference materials and reference measurement systems in laboratory medicine. Transfer of values to reference materials.

For concentration values assigned to reference and proficiency testing materials, and to patient samples, to be traceable to those in recognised, authoritative reference materials, the value must be transferred from these materials by precise methods. The intent of this document is to outline guidelines for transfer of values from a higher to a lower level reference material, e.g. from primary to secondary4) and from secondary to working reference materials. The guidelines are intentionally broad and relatively non-specific; they may still require revision for specific analytes.

Chemistry, Clinical↗
PubMed1994

Antibody to herpes simplex virus type 2 as serological marker of sexual lifestyle in populations.

OBJECTIVES: To examine the epidemiology of antibody to herpes simplex virus type 2 and to assess its suitability as a serological marker of sexual behaviour in populations with high and low prevalences. DESIGN: Cross sectional survey. SETTING: Department of genitourinary medicine and blood donation centre in central London. SUBJECTS: Representative sample of 869 patients attending department between November 1990 and December 1991, and 1494 consecutive blood donors attending for donation between February and April 1992. METHOD: Participants had a blood sample taken for antibody testing with a novel type specific assay and completed a questionnaire. RESULTS: Prevalence of antibody differed significantly between the two groups (188/833 (22.7%) clinic attenders; 102/1347 (7.6%) blood donors). In both populations antibody was strongly associated with sex, sexual orientation, years of sexual activity, number of lifetime sexual partners, and past infection with sexually transmitted diseases after other factors were controlled for. Only 130 (45%) of all those with antibody had symptoms suggestive of genital herpes, and 79 (27.4%) had had genital herpes diagnosed. Of those without antibody to herpes simplex viruses type 1 and 2, 8.0% reported genital blisters or sores and 1.1% had had genital herpes diagnosed by a doctor. CONCLUSIONS: The strong relation between herpes simplex virus type 2 and sexual lifestyle suggests that the presence of antibody to the virus may be suitable for use as an objective, serological marker of patterns of sexual behaviour in different populations. These data show that only a minority of those infected with herpes simplex virus type 2 have a diagnosis of genital herpes or express clinical symptoms, making serological determinants of infection essential for epidemiological studies.

Adolescent↗
PubMed1994

Survival differences in European patients with AIDS, 1979-89. The AIDS in Europe Study Group.

OBJECTIVES: To examine the pattern of survival and factors associated with the outcome of disease in patients with AIDS. DESIGN: Inception cohort. Data collected retrospectively from patients' charts. SETTING: 52 clinical centres in 17 European countries. SUBJECTS: 6578 adults diagnosed with AIDS from 1 January 1979 to 31 December 1989. MAIN OUTCOME MEASURES: Survival after the time of diagnosis. RESULTS: The median survival after diagnosis was 17 months, with an estimated survival at three years of 16% (95% confidence interval 15% to 17%). Patients diagnosed in southern Europe had a shorter survival, particularly immediately after the time of diagnosis, compared with patients diagnosed in central and northern Europe (survival at one year (95% confidence interval) 54% (52% to 56%) 66% (64% to 68%), 65% (63% to 66%), respectively. The three year survival, however, was similar for all regions. The regional differences in survival were less pronounced for patients diagnosed in 1989 compared with earlier years. Improved survival in recent years was observed for patients with a variety of manifestations used to define AIDS but was significant only for patients diagnosed with Pneumocystis carinii pneumonia. The three year survival, however, remains unchanged over time. CONCLUSIONS: Survival of AIDS patients seems to vary within Europe, being shorter in southern than central and northern Europe. The magnitude of these differences, however, has declined gradually over time. Short term survival has improved in recent years, but the long term prognosis has remained equally poor, reflecting the fact that the underlying infection with HIV and many of the complicating diseases remains essentially uncontrolled.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Comparison of long-term prognosis of patients with AIDS treated and not treated with zidovudine. AIDS in Europe Study Group.

OBJECTIVE: To determine the association between elapsed time since starting zidovudine and survival in patients with acquired immunodeficiency syndrome (AIDS). DESIGN: Inception cohort and observational study of patients treated and not treated with zidovudine. SETTING: Fifty-one centers in 17 European countries. PATIENTS: A total of 4484 patients diagnosed as having AIDS from 1979 to 1989 who survived their initial AIDS-defining event and who had not started zidovudine before AIDS diagnosis. MAIN OUTCOME MEASURES: Use of zidovudine and mortality. RESULTS: Among patients who did not receive zidovudine, the death rate was approximately constant for the first 5 years after AIDS diagnosis. For patients treated with zidovudine, the death rate within the first year since starting zidovudine was markedly lower than for untreated patients who had developed AIDS at the same time (relative rate, 0.47; 95% confidence interval [CI], 0.42 to 0.51). For longer times since starting zidovudine, the association with reduced mortality rate was diminished, and for patients surviving more than 2 years since starting zidovudine, the death rate was greater than for untreated patients who had developed AIDS at the same time (relative rate, 1.35; 95% CI, 1.15 to 1.58). Adjustment for other prognostic factors failed to substantially affect this observation. CONCLUSIONS: When initiated after the time of AIDS diagnosis, zidovudine was associated with improved prognosis but for no more than 2 years after starting therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Apolipoproteins and ischaemic heart disease: implications for screening.

Apolipoproteins and lipids are established risk factors of ischaemic heart disease (IHD) but their efficacy as screening tests is not known. We therefore examined the mortality from IHD and serum concentrations of lipids and apolipoproteins in a prospective study of 21,520 men aged 35-64 years. Serum apo B was the apolipoprotein most strongly associated with IHD risk; a decrease in apo B of 10% was associated with 22% lower risk of IHD. However, measurement of apo B alone detected only 17% of all IHD deaths at the cost of a 5% false-positive rate. Combining apo B with apo AI and apo (a) increased the detection rate to 19%. With systolic blood pressure, smoking, and family history of IHD the detection rate increased to 28%. We conclude that screening for IHD by measuring apo B alone or with apo AI and apo (a) is too poor to discriminate between recommending drug therapy or lifestyle change for some and not others. It is not advisable to screen for IHD by measuring any combination of cholesterol, apo B, apo AI, apo (a) and the other risk factors. The primary aim in prevention of ischaemic heart disease should be to lower the risk factors in the population.

Adult↗
PubMed1994

An empirical comparison of distance matrix techniques for estimating codon usage divergence.

The quantitative description of codon usage divergence among taxa is a two-step process involving first the calculation of a standardized measure of intertaxon divergence for each possible pair of taxa followed by a summary and visual display of the patterns among the taxa inherent in these measures. Three different measures have been proposed in the literature, and three different summaries have been used. These different techniques are empirically compared using a data set consisting of gene sequences from seven species of Apicomplexa. The results suggest that the manhattan distance measure may be preferable to the use of the chi-square measure, although the separation of amino acid usage and codon usage by the genetic distance produces theoretical advantages. The multidimensional scaling ordination and unweighted pair-group clustering are both successful in displaying the patterns, while the eigenanalysis ordination is not.

Animals↗