Cushing's syndrome in a 16 year old girl due to ectopic ACTH precursor production from a pancreatic tumour.
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Adolescent↗
Biomedical subjects
J A Thomson
Publications and source records attributed to J A Thomson.
Human embryonic stem cell technology.
Undifferentiated human embryonic stem (ES) cells can be cultured indefinitely and yet maintain the potential to form almost every cell in the adult human body. Therefore ES cells provide a model for understanding the differentiation and function of human tissue, offer new strategies for drug discovery and testing, and have the potential to provide new transplantation therapies for the treatment of a wide variety of human diseases. In this article, we describe the origin and properties of human ES cells, distinguish ES cells from other pluripotent stem cell lines, and discuss their implications for basic research and human medicine.
Animals↗
Biocontrol of the sugarcane borer Eldana saccharina by expression of the Bacillus thuringiensis cry1Ac7 and Serratia marcescens chiA genes in sugarcane-associated bacteria.
The cry1Ac7 gene of Bacillus thuringiensis strain 234, showing activity against the sugarcane borer Eldana saccharina, was cloned under the control of the tac promoter. The fusion was introduced into the broad-host-range plasmid pKT240 and the integration vector pJFF350 and without the tac promoter into the broad-host-range plasmids pML122 and pKmM0. These plasmids were introduced into a Pseudomonas fluorescens strain isolated from the phylloplane of sugarcane and the endophytic bacterium Herbaspirillum seropedicae found in sugarcane. The ptac-cry1Ac7 construct was introduced into the chromosome of P. fluorescens using the integration vector pJFF350 carrying the artificial interposon Omegon-Km. Western blot analysis showed that the expression levels of the integrated cry1Ac7 gene were much higher under the control of the tac promoter than under the control of its endogenous promoter. It was also determined that multicopy expression in P. fluorescens and H. seropedicae of ptac-cry1Ac7 carried on pKT240 caused plasmid instability with no detectable protein expression. In H. seropedicae, more Cry1Ac7 toxin was produced when the gene was cloned under the control of the Nm(r) promoter on pML122 than in the opposite orientation and bioassays showed that the former resulted in higher mortality of E. saccharina larvae than the latter. P. fluorescens 14::ptac-tox resulted in higher mortality of larvae than did P. fluorescens 14::tox. An increased toxic effect was observed when P. fluorescens 14::ptac-tox was combined with P. fluorescens carrying the Serratia marcescens chitinase gene chiA, under the control of the tac promoter, integrated into the chromosome.
Animals↗
Introduction of the Serratia marcescens chiA gene into an endophytic Pseudomonas fluorescens for the biocontrol of phytopathogenic fungi.
An endophytic strain of Pseudomonas fluorescens was isolated from micropropagated apple plantlets and introduced into beans (Phaseolus vulgaris) via their root tips. It was shown to be present as an endophyte in the roots at a level of 1.2 x 10(5) CFU/g fresh weight. The gene coding for the major chitinase of Serratia marcescens, chiA, was cloned under the control of the tac promoter into the broad-host-range plasmid pKT240 and the integration vector pJFF350. Pseudomonas fluorescens carrying tacchiA either on the plasmid or integrated into the chromosome is an effective biocontrol agent of the phytopathogenic fungus Rhizoctonia solani on bean seedlings under plant growth chamber conditions.
Chitinases↗
Fatal lymphoproliferative disease associated with a novel gammaherpesvirus in a captive population of common marmosets.
BACKGROUND AND PURPOSE: Callitrichids (marmosets and tamarins) are extremely susceptible to experimental tumor induction by herpesviruses native to other primate species. A colony of common marmosets developed a syndrome of weight loss, inappetence, diarrhea, and in several animals, palpable abdominal masses. METHODS: Marmosets in the colony were subjected to histologic examination and serologic testing for Epstein-Barr virus (EBV). The DNA from tumors that developed in the marmosets was subjected to consensus primer polymerase chain reaction (PCR) analysis designed to amplify conserved regions of herpesvirus genomes. RESULTS: The mesenteric lymph nodes and intestinal mucosa were consistently infiltrated by principally B lymphocytes, which often obliterated the normal architecture. Of 84 clinically normal marmosets, 52 were seropositive for EBV. The tumor DNA contained previously unreported herpesvirus sequences closely related to but distinct from those of EBV, Herpesvirus papio, and these lymphocryptovirus, a novel gammaherpesvirus. Results of PCR analysis of circulating lymphocytes from EBV-positive, clinically normal marmosets were negative for EBV antibodies and were positive for marmoset lymphocryptovirus; PCR analysis of circulating lymphocytes from EBV-negative marmosets yielded negative results for EBV and this novel marmoset lymphocryptovirus. CONCLUSION: This novel gammaherpesvirus possibly associated with tumor development may have important management implications for captive callitrichids.
Amino Acid Sequence↗
Validation of short tandem repeat analysis for the investigation of cases of disputed paternity.
This study details validation of two separate multiplex STR systems for use in paternity investigations. These are the Second Generation Multiplex (SGM) developed by the UK Forensic Science Service and the PowerPlex 1 multiplex commercially available from Promega Inc. (Madison, WI, USA). These multiplexes contain 12 different STR systems (two are duplicated in the two systems). Population databases from Caucasian, Asian and Afro-Caribbean populations have been compiled for all loci. In all but two of the 36 STR/ethnic group combinations, no evidence was obtained to indicate inconsistency with Hardy-Weinberg (HW) proportions. Empirical and theoretical approaches have been taken to validate these systems for paternity testing. Samples from 121 cases of disputed paternity were analysed using established Single Locus Probe (SLP) tests currently in use, and also using the two multiplex STR systems. Results of all three test systems were compared and no non-conformities in the conclusions were observed, although four examples of apparent germ line mutations in the STR systems were identified. The data was analysed to give information on expected paternity indices and exclusion rates for these STR systems. The 12 systems combined comprise a highly discriminating test suitable for paternity testing. 99.96% of non-fathers are excluded from paternity on two or more STR systems. Where no exclusion is found, Paternity Index (PI) values of > 10,000 are expected in > 96% of cases.
Asian People↗
Generation of maize cell lines containing autonomously replicating maize streak virus-based gene vectors.
Virion sense gene replacement derivatives of maize streak virus (MSV) were constructed with selectable marker expression cassettes based on the bialaphos resistance gene (bar) and the CaMV 35S promoter. The effect on replication of increasing the genomic size was tested by including: (1) the 550-bp maize adhI intron and 68-bp TMV omega RNA leader sequences upstream of the bar genes; and (2) a fusion between the bar and E. coli glutathione reductase (gor) genes. Three recombinant viral vectors ranging in size from 2.7 kb to 4.8 kb replicated efficiently in biolistically transfected cells of suspension cultured Black Mexican sweetcorn (BMS) cells. Deletions greater than 39 bp 3' of the stemloop sequence in the LIR adversely affected replicon release. Transformed bialaphos-resistant BMS cell lines were generated with all three vectors containing the bar gene: between 38 and 60% of cell lines contained replicating viral episomes. The replicons were structurally stable, replicated to copy numbers of over 500 per haploid genome, and were detected for more than one year after introduction. We noted significant enhancement of bar gene expression, both at the protein and RNA levels, associated with the presence of episomal vector DNA. The maize adhI intron and TMV omega RNA leader sequences did not seem to have a significant effect on bar gene expression from replicating constructs, although expression from controls was enhanced. The results suggest that MSV-based constructs would provide a useful system for long-term gene amplification in cereal cell culture systems.
Acetyltransferases↗
Assessment of long-term outcomes of hepatitis C virus infection in a cohort of patients with acute hepatitis in 1971-1975: results of a pilot study.
BACKGROUND: To examine the long-term effects of hepatitis C virus (HCV) infection in a cohort of patients admitted to Fairfield Hospital with hepatitis from 1971 to 1975. The availability of stored sera from this time enabled testing to identify those who were anti-HCV positive on admission. METHODS: Sixteen per cent (n = 230) of the cohort tested positive for HCV antibody (anti-HCV). The 'unexposed' group was selected from those who were anti-HCV negative. Systematic approaches were used to locate the cohort and health outcomes assessed by a study specific questionnaire and clinical review with repeat serology and liver function tests. RESULTS: Complete follow up has been achieved on a subset of 35 HCV-seropositive and 70 seronegative individuals. The seropositive group was significantly more likely to have given a history of injecting drug use, the presumed route of infection. The seropositive group was also more likely to have elevated serum alanine aminotransferase levels, but only two (6%) were known to have progressed to cirrhosis. DISCUSSION: The anti-HCV-positive individuals followed up to date are at increased risk of liver-related pathology, but few had progressed to cirrhotic liver disease. This differs from findings of transfusion-related studies and suggests, within the limitations of the study, that the natural history of community acquired HCV may be more benign.
Acute Disease↗
Embryonic stem cell lines derived from human blastocysts.
Human blastocyst-derived, pluripotent cell lines are described that have normal karyotypes, express high levels of telomerase activity, and express cell surface markers that characterize primate embryonic stem cells but do not characterize other early lineages. After undifferentiated proliferation in vitro for 4 to 5 months, these cells still maintained the developmental potential to form trophoblast and derivatives of all three embryonic germ layers, including gut epithelium (endoderm); cartilage, bone, smooth muscle, and striated muscle (mesoderm); and neural epithelium, embryonic ganglia, and stratified squamous epithelium (ectoderm). These cell lines should be useful in human developmental biology, drug discovery, and transplantation medicine.
Animals↗
The prevalence of hepatitis C in patients admitted with acute hepatitis to Fairfield Infectious Diseases Hospital, 1971-1975.
OBJECTIVE: To identify and determine trends in the prevalence of hepatitis C virus (HCV) antibody in stored sera from 1971 to 1975 and to determine associations with HCV seropositivity, including markers for other hepatitis infections and possible routes of transmission. DESIGN: A retrospective cross-sectional study. PATIENTS AND SETTING: 1511 adults admitted to Fairfield Infectious Diseases Hospital, Victoria, with a clinical and biochemical diagnosis of hepatitis between 1 January 1971 and 31 December 1975. MAIN OUTCOME MEASURES: Prevalence over study period of hepatitis A virus antibody (anti-HAV) IgM, hepatitis B core antibody (anti-HBc), hepatitis B surface antigen (HBsAg) and hepatitis C virus antibody (anti-HCV) in stored sera; sociodemographic data and risk factors for blood-borne viruses documented in original medical records. RESULTS: Anti-HCV was detected in 17% of adults admitted with hepatitis from 1971 through 1975. Prevalence increased significantly over this period. Most cases were in young men who had a history of injecting drug use. HCV seropositivity was also significantly associated with markers for hepatitis B infection. CONCLUSIONS: Given the 20-30-year period between infection with hepatitis and the development of liver disease, our findings predict significant liver-related morbidity in Australia in the next decade. The increase in prevalence over the five years studied suggests rapid spread of HCV through susceptible populations, principally injecting drug users.
Acute Disease↗
Hepatitis C virus NS3 RNA helicase domain with a bound oligonucleotide: the crystal structure provides insights into the mode of unwinding.
BACKGROUND: Hepatitis C virus (HCV) represents a major health concern as it is responsible for a significant number of hepatitis cases worldwide. Much research has focused on the replicative enzymes of HCV as possible targets for more effective therapeutic agents. HCV NS3 helicase may provide one such suitable target. Helicases are enzymes which can unwind double-stranded regions of DNA or RNA in an ATP-dependent reaction. The structures of several helicases have been published but the structural details as to how ATP binding and hydrolysis are coupled to RNA unwinding are unknown. RESULTS: The structure of the HCV NS3 RNA helicase domain complexed with a single-stranded DNA oligonucleotide has been solved to 2.2 A resolution. The protein consists of three structural domains with the oligonucleotide lying in a groove between the first two domains and the third. The first two domains have an adenylate kinase like fold, including a phosphate-binding loop in the first domain. CONCLUSIONS: HCV NS3 helicase is a member of a superfamily of helicases, termed superfamily II. Residues of NS3 helicase which are conserved among superfamily II helicases line an interdomain cleft between the first two domains. The oligonucleotide binds in an orthogonal binding site and contacts relatively few conserved residues. There are no strong sequence-specific interactions with the oligonucleotide bases.
Amino Acid Sequence↗
Colon cancer in aged captive rhesus monkeys (Macaca mulatta).
The age-related incidence of malignant neoplasia was surveyed from a total of 301 necropsy cases of rhesus monkeys ranging in age from 13-37 years performed in the Pathology Service Unit of the Wisconsin Regional Primate Research Center during the past 15 years. All our aged monkeys lived in indoor cages and were fed with monkey chow and supplemental fruits during the past decades. In this survey, we found a total of 51 malignant neoplasms, and among them 25 cases were colon cancer. The incidence of colon cancer increased with advancing age: 3.2% at 13-19 years, 9.2% at 20-25 years, 13.5% at 26-29 years, and 20.7% at 30-37 years. Most cancers were located in the cecum and transverse regions with a unicentric origin. Two multicentric cases were associated with chronic hypertrophic colitis. Precancerous polypous lesions were not found in all cases. Histologically, all cases were mucinous adenocarcinoma and had local invasion to the muscular wall. Metastasis to the mesenteric lymph nodes was found in only two cases. As in humans, colon cancer is a common outcome of aging in nonhuman primates.
Adenocarcinoma, Mucinous↗
Isolation and characterisation of an aryl-beta-D-glucoside uptake and utilisation system (abg) from the gram-positive ruminal Clostridium species C. longisporum.
A phosphotransferase-dependent aryl-beta-glucoside uptake and utilisation system (abg) was isolated from the ruminal Clostridium ("C. Longisporum"). The system is composed of three genes, abgG, abgF and abgA, and a number of regulatory regions, including terminator/antiterminator type stem-loop structures preceding the abgG and abgF genes. Similarity analysis of the proteins encoded by these genes indicated that they were responsible for the regulation of the abg system through antitermination (AbgG), the uptake and phosphorylation of aryl-beta-glucosides (AbgF) and the hydrolysis of the intracellular phosphorylated glycosides (AbgA). Experimental evidence for the functions of AbgF and AbgA was obtained. Although it was not possible to demonstrate any function for AbgG, a promoter 5' to the abgG gene was identified which was responsible for expression of the downstream genes. The abg system is remarkably similar to operons from the gram negative Enterobacteriaceae, both in the coding and non-coding regulatory regions.
Amino Acid Sequence↗
Primate embryonic stem cells.
Primate embryonic stem (ES) cells are derived from preimplantation embryos, have a normal karyotype, and are capable of indefinite, undifferentiated proliferation. Even after culture for more than a year, primate ES cells maintain the potential to differentiate to trophoblast and derivatives of embryonic endoderm, mesoderm, and ectoderm. In this review, we compare the characteristics of ES cell lines from two primate species, the rhesus monkey (Macaca mulatta) and the common marmoset (Callithrix jacchus), with the characteristics of mouse ES cells and human embryonal carcinoma cells. We also discuss the implications of using primate ES cells to understand early human development and discuss the practical and ethical implications for the understanding and treatment of human disease.
Animals↗
Automatic spatial updating during locomotion without vision.
People can update their spatial relationships relative to the environment while walking without vision. The hypothesis that such updating is automatic was tested in a locomotor task in which the subjects were asked to refrain from updating their positions. Subjects walked without vision to one of four previously seen targets via a second location. In one condition--the updating condition--the subjects were asked to walk to the real position of the target relative to the second location; in another--the ignoring condition--they were asked to imagine that they had not moved from the starting point and to walk from the second location as if walking to the target from the initial location. When the subjects were asked to start walking to the target as soon as it was named by the experimenter, they performed better in the updating condition than in the ignoring condition. When the subjects were allowed more time to respond, the difference in performance between these two conditions disappeared. The results suggest that the subjects automatically updated their positions as they moved, but that, given enough time, they could override this updating retrospectively using more deliberate cognitive processing.
Automatism↗
Hepatitis A vaccination of child care workers in Victoria: are recommendations being implemented?
This study examined the self-reported hepatitis A and B immunisation status of child care workers, the level of awareness among child care workers of the NHMRC recommendation for immunisation against hep. A and centre practices. A confidential mail survey was conducted in June 1996 with workers and co-ordinators from 113 randomly selected child care centres. Co-ordinators completed a questionnaire on the centre's characteristics and immunisation policy. Child care workers completed a second questionnaire on their immunisation knowledge or beliefs and immunisation status. Ninety-five centres (85%) and 607 (74%) workers participated. Only 11% of workers were vaccinated against hep. A, although the majority of child care worker respondents believed their occupation placed them at increased risk. Those vaccinated were more likely to be aware of the availability of hep. A vaccine, of the NHMRC recommendation for hep. A vaccination, and to have been vaccinated for hep. B. Centres in which co-ordinators perceived hep. A vaccination as important, and those which recorded staff immunisation, particularly hep. A, were more likely to have child care workers who were vaccinated against hep. A. In contrast, nearly two-thirds of child care workers reported that they were vaccinated against hep. B, although hep. B is not routinely recommended by the NHMRC for child care workers. These findings show a need for further policy and educational initiatives in the implementation of an immunisation strategy for child care workers.
Adult↗
Neural differentiation of rhesus embryonic stem cells.
Primate embryonic stem (ES) cells are capable of indefinite, undifferentiated proliferation and maintain the potential to differentiate to trophoblast and derivatives of embryonic endoderm, mesoderm, and ectoderm. We previously reported that neural differentiation by rhesus ES cells in teratomas includes tissue with a remarkable resemblance to neural tube (Thomson et al. 1995). Here we examine a series of markers including a cell proliferation marker, neurofilament proteins, and glial fibrillary acidic protein (GFAP) in teratomas at 5, 6, 7, 9, and 12 weeks after rhesus ES cell transplantation into muscles of immunodeficient mice. All teratomas examined contained derivatives of all three embryonic germ layers. Neural differentiation included tissues resembling neural tube and embryonic ganglia, as well as individual dispersed neurons, and brain-like gray matter. Tumours of all ages contained neurons and proliferating cells, indicated by staining for neurofilament subunits and Ki67 antigens. Younger tumours contained no or few astrocytes indicated by the absence of GFAP staining, but as these tumours developed, there was an increase in astrocyte differentiation. The results indicate that normal neural differentiation is recapitulated, in part, by the differentiation of rhesus ES cells in teratomas. The differentiation of rhesus ES cells provides an important new model for understanding human neural differentiation.
Animals↗
The effectiveness of parents in promoting the development of road crossing skills in young children.
BACKGROUND: Young children show poor judgment when asked to select a safe place to cross the road, frequently considering dangerous sites to be safe. Correspondingly, child pedestrian accidents are over-represented at such locations. Increasing the child's ability to recognise such dangers is a central challenge for road safety education. AIMS: Practical training methods have proved effective in improving such judgments but are labour-intensive, time-consuming and therefore difficult to implement on a realistic scale. The study examined the possibility that volunteers from the local community might be capable of using such methods to promote children's pedestrian competence. SAMPLE: Sixty children from the Primary 1 (Reception) classes of three Glasgow schools took part. Volunteers were ordinary parents from the same areas. None had 'formal' experience of working with children other than through being parents. METHOD: Volunteers received experience of training children at courses organised in each school. Children learned in small groups, receiving two sessions of roadside training followed by four on a table-top model. Pre- and post-tests allowed the effectiveness of training to be assessed. RESULTS: Significant improvements relative to controls were found in all children following training. Improvements proved robust and no deterioration was observed two months after the programme ended. Comparison with a previous study in which training was undertaken by highly qualified staff showed that the volunteers were as effective as 'expert' trainers. CONCLUSIONS: Parent volunteers can significantly increase the pedestrian competence of children as young as five years. They constitute a most valuable 'resource' in road safety education. The opportunities afforded by involving the local community in educational interventions should be further explored.
Accidents, Traffic↗