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Biomedical subjects

S Edwards

Publications and source records attributed to S Edwards.

At least 19 recordsLinked to original sources
PubMed2026

Two iPSC lines with frameshift mutations in FTSJ1 as models for X-linked non-syndromic intellectual disability.

CRISPR/Cas9 was used to introduce two different FTSJ1 frameshift mutations into an existing human male iPSC line (UMGWi004-B). No additional genomic or chromosomal changes were detected. The modified iPSC express different stem cell markers and can be induced to differentiate into cells from all three germ layers. FTSJ1 is ubiquitously expressed and mutations in this X-chromosomal gene are involved in an intellectual developmental disorder (OMIM: #309549). These cells can be used to model the disease at the cellular and organoid level in their original state or after differentiation into cell types of interest.

Journal Article↗
PubMed1992

Isolation of a Lelystad virus-like agent from British pigs and scanning electron microscopy of infected macrophages.

Six, one-week-old gnotobiotic piglets were inoculated with tissues or sera collected from field cases of porcine reproductive and respiratory syndrome. The piglets showed little or no illness, and two that were necropsied at 8 and 9 days post infection appeared grossly normal. However, a Lelystad virus-like agent was isolated from most of the inoculated pigs using porcine alveolar macrophage cultures. Seroconversion to the Lelystad virus was observed and some animals developed microscopically detectable interstitial pneumonias. Scanning electron microscopy was used to study the in vitro cytopathic effect of the Lelystad virus on porcine alveolar macrophages.

Abortion, Veterinary↗
PubMed1992

Characterisation of p20 gene sequences from a border disease-like pestivirus isolated from pigs.

A pestivirus, isolated from pigs with haemorrhagic lesions, was antigenically more similar to border disease (BD) virus than to either hog cholera (HC) or bovine viral diarrhoea (BVD) viruses. After reverse transcription the genome at the 5' end, along with the same region from a BD isolate from sheep, was amplified by the polymerase chain reaction and cloned. The region of the p20 gene was sequenced and compared with published data for BVD and HC viruses. A number of motifs were conserved in the amino acid sequences of all the viruses. The pig isolate had a greater degree of homology in this region with the BD isolate (87%) than with BVD (73%) or HC (74%) viruses. This further confirms the BD-like nature of the virus.

Amino Acid Sequence↗
PubMed1992

An experimental model for myocarditis and congestive heart failure after rabbit coronavirus infection.

In a model for virus-induced myocarditis and congestive heart failure, rabbit coronavirus infection was divided into acute (days 2-5) and subacute (days 6-12) phases on the basis of day of death and pathologic findings. During the acute phase, the principal histologic lesions were degeneration and necrosis of myocytes, myocytolysis, interstitial edema, and hemorrhage. The severity of these changes increased in the subacute phase. Pleural effusion and congestion of the lungs and liver were also present at this time. Myocarditis was detected by day 9 and peaked by day 12. Heart weights and heart weight-to-body weight ratios were increased, and dilation of the right ventricular cavity became prominent early in infection and persisted. In contrast, dilation of the left ventricle occurred late in the subacute stage. Virus was isolated from infected hearts between days 2 and 12. These data suggest that rabbit coronavirus infection progresses to myocarditis and congestive heart failure.

Animals↗
PubMed1992

An experimental model for dilated cardiomyopathy after rabbit coronavirus infection.

A rabbit model for coronavirus-induced dilated cardiomyopathy is described. Acute rabbit coronavirus infection results in virus-induced myocarditis and congestive heart failure. Of the survivors of rabbit coronavirus infection, 41% had increased heart weight and heart weight-to-body weight ratios, biventricular dilation, myocyte hypertrophy, myocardial fibrosis, and myocarditis consistent with the development of dilated cardiomyopathy. These changes were also seen in the remaining 59% of the survivors, except that the degree of myocyte hypertrophy was reduced and only right ventricular dilation was present. In most survivors, myocarditis was usually mild (1-5 foci/transverse section), but in some cases it was severe (> 20 foci/transverse section). Interstitial and replacement fibrosis was more pronounced in the papillary muscles. These data suggest that rabbit coronavirus infection may progress to dilated cardiomyopathy.

Animals↗
PubMed1991

Mycobacterium bovis infection in human beings in contact with elk (Cervus elaphus) in Alberta, Canada.

Human infection with Mycobacterium bovis is rare in developed countries because of milk pasteurisation and the slaughter of infected cattle. An epizootic of M bovis infection in domesticated elk (Cervus elaphus) in Alberta, Canada, which started in April, 1990, prompted us to seek human contacts of elk herds. There were 446 identified contacts, in 394 of whom tuberculin skin tests were done. Of 81 contacts who were skin-test positive, 50 had been in contact with culture-positive animals. 6 of 106 subjects tested a second time became tuberculin positive. 1 case of active M bovis infection was diagnosed by sputum culture. The mode of transmission of M bovis from these farm animals to man is likely to be aerosolisation of infected particles. Because of the apparent susceptibility of farmed Cervidae (deer) to M bovis infection, and the evidence of spread to man, control measures to prevent human infection should be developed.

Adult↗
PubMed1991

Mycobacterium bovis infection in humans exposed to elk in Alberta.

The evidence of zoonotic transmission of M. bovis infection in the 1 veterinarian is confirmed by growth of the organism from his sputum 6 months after animal contact. The high rate of initial tuberculin reactivity and the skin test conversions of 6 persons in contact with culture-positive animals strongly suggest that further human infection has taken place. However, the lack of baseline testing on 48/81 test-positive individuals and the relatively high proportion of immigrants in some occupational groups makes it impossible to determine the extent of reactivity and infection that can be attributed to handling diseased elk. The method of spread is likely by aerosolization of infected particles produced from the cough of live animals, or by the housing of infected material in the rendering plant or postmortem laboratory. Although isoniazid prophylaxis has not been demonstrated to be protective against M. bovis reactivation disease, it seems reasonable to offer the drug to those contacts who are newly infected. Follow-up of human contacts of animal tuberculosis must be carried out.

Adult↗
PubMed1991

Transmission of bovine virus diarrhoea virus by blood feeding flies.

Three species of blood-feeding flies (Stomoxys calcitrans, Haematopota pluvialis and Hydrotaea irritans) were fed for five minutes on a bullock persistently infected with bovine virus diarrhoea virus (BVDV) containing 10(4.5)TCID50 non-cytopathic BVDV/ml serum, then subsequently fed on BVDV-free seronegative animals maintained in isolation. Virus was isolated from recipient animals between days 5 and 10 using H pluvialis, and up to 72 hours after transmission with S calcitrans; virus isolation was negative using H irritans. Positive seroconversion results obtained with H pluvialis gave a steadily increasing antibody titre. BVDV was recovered from flies 96 hours (four days) after an infective feed for H pluvialis and S calcitrans, but for two hours only for H irritans.

Animals↗
PubMed1991

The effect of inducing agents on the numbers of interphase fibrillar centers in the U937 promonocytic cell line.

The mean numbers of interphase fibrillar centers have been determined in triplicate experiments, using the argyrophil (AgNOR) method. Promonocytic U937 cells were incubated with each of three inducing agents, namely, interleukin-6, granulocyte-macrophage colony-stimulating factor, and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate. The cells were examined at 24, 48, and 72 h during the induction periods and their doubling time and mean AgNOR score were calculated. After 72 h, the cells were maintained in culture for a further 24 h in the absence of an inducing agent and these parameters were determined again. It was found that whereas the unstimulated U937 cells had a mean value in the region of 50 AgNORs per nucleus, this diminished to about 20 after a 72 h incubation, but rose to 30 or more when the inducing agents had been withdrawn for 24 h. These observation confirm the results of previous studies using melanoma and HL60 cell lines: however, it has now been demonstrated that a variety of agents can modulate the numbers of fibrillar centers in a very similar way in a single cell line. Furthermore, we have shown that the "undifferentiated" U937 cell AgNOR score recovers when the agents no longer act upon the cells; this implies that fibrillar center numbers are intimately related to differentiation state in cell lines, as in the case in, for example, tumor specimens.

Cell Count↗
PubMed1991

Peripherally administered 5-hydroxytryptamine elicits the full behavioural sequence of satiety.

If 5-HT acts as a peripheral satiety signal, then it should not only produce anorectic effects when administered systemically but should allow the normal behavioural sequence of satiety to develop. Food-deprived rats treated with 5 mg/kg 5-HT were found to show, when given access to food, the full normal behavioural sequence of satiety, although the sequence occurred earlier than in rats treated with saline. It is therefore argued that 5-HT must be considered as a likely candidate for a peripheral satiety signal.

Animals↗
PubMed1991

The development of an international reference panel of monoclonal antibodies for the differentiation of hog cholera virus from other pestiviruses.

A panel of 30 monoclonal antibodies was defined and characterized with respect to the binding capacity in immunoperoxidase assay to different strains of pestivirus. Using the panel it was possible to identify specifically all strains and isolates of hog cholera virus, hog cholera vaccines derived from 'C' strains, and most strains of bovine viral diarrhoea/border disease (BVD/BD) viruses (including those isolated from pigs). A small proportion of BVD/BD isolates from pigs and ruminants reacted only with the monoclonals specific for pestivirus group antigen. It is recommended that monoclonal typing methods be introduced into official procedures for the diagnosis of hog cholera/classical swine fever.

Animals↗
PubMed1991

Chronic bullous disease of childhood with oral mucosal scarring.

Chronic bullous disease of childhood (CBDC) is an acquired subepidermal bullous disease; oral involvement occurs with mouth ulcers and blisters in 57% of patients. The condition usually remits before puberty but persistence of the disease in adulthood is recognized. We report a case with severe oral scarring similar to that described in patients with adult linear IgA disease. To our knowledge this has not been previously described.

Child↗
PubMed1991

Demonstration of insulin transformation products in insulin vials by high-performance liquid chromatography.

OBJECTIVE: To assess the importance of temperature, light, agitation, and regular withdrawal of insulin on the rates of appearance of three groups of insulin transformation products (ITPs) in vials of human and beef soluble insulin. RESEARCH DESIGN AND METHODS: Twelve insulin-treated patients (6 receiving human soluble insulin, 6 receiving beef soluble insulin) participated in the study. Reverse-phase high-performance liquid chromatography was used to measure ITP in serial samples from vials stored in various laboratory environments or issued to patients. Vials in the laboratory were analyzed on nine occasions over 26 wk; those issued to patients were analyzed weekly. RESULTS: Results were expressed as rates of change (% total protein/wk). Except for human insulin stored at 4 degrees C, sampling did not accelerate transformation. Storage at higher temperatures caused more rapid transformation to all ITP groups, and human insulin was more susceptible than beef insulin. Exposure to light accelerated transformation mainly to group 3 ITP. Fibrillation occurred in beef but not human insulin carried in a shirt pocket. Results from patients' vials were consistent with reported storage conditions. CONCLUSIONS: All three ITP groups form in human and beef soluble insulin. Their rate of production is a function of temperature and light exposure. Differences between the two insulins were probably due to differences in formulation. Patients should be discouraged from hoarding vials and storing insulin in direct sunlight. One or more ITPs could contribute to the residual immunogenicity of modern insulin preparations.

Analysis of Variance↗
PubMed1991

The effect of class II gene transfection on the tumourigenicity of the H-2K-negative mouse leukaemia cell line K36.16.

There is much evidence to suggest that potentially immunogenic tumour cells can escape cytolytic immune destruction by loss of class I antigen expression. Many tumours are allele-specific class I negative and, in murine systems, reconstitution of class I expression by gene transfection leads to an increase in tumour immunogenicity. In many systems where mice have rejected class I transfected tumour cells they are also immune to a subsequent challenge with the untransfected parent tumour. In this study we have examined the effect of stable class II antigen expression (induced by gene transfection) on a class I loss mutant (H-2Kk negative) murine cell line, K36.16. We show that H-2Ek expression is more effective at increasing tumour immunogenicity than the reconstitution of H-2Kk expression in these cells. This suggests that the induction of class II antigen expression on tumour cells may provide an effective way of enhancing tumour-specific immune responses in vivo.

Animals↗
PubMed1991

Immunomagnetic purging of breast cancer from bone marrow for autologous transplantation.

Intensive chemotherapy with autologous bone marrow transplantation is a promising approach for the treatment of breast cancer, provided that clonogenic tumor cells do not contaminate the patient's bone marrow. We have previously demonstrated that a combination of 4-hydroperoxycyclophosphamide (4-HC) and immunomagnetic purging (IMP) with monoclonal antibodies and microspheres could remove 4-5 logs of clonogenic breast cancer cells from a 10-fold excess of human bone marrow cells. In the present report we have evaluated an apparatus for separating tumor cells from a large volume of human marrow. This apparatus will permit preparation of large volumes of purged marrow for use in studies of intensive therapy with autologous marrow support. Bone marrow progenitor cell (CFU-GM) recovery following this IMP technique was 85% of the unpurged control, and suggests that marrow recovery following high dose systemic chemotherapy will not be adversely affected. A phase I study to evaluate marrow reconstitution following IMP is underway. Preliminary data suggest that this IMP method will not delay engraftment in breast cancer patients receiving high-dose chemotherapy and autologous bone marrow support, but further study is required.

Adenocarcinoma↗