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Biomedical subjects

I Scott

Publications and source records attributed to I Scott.

At least 55 records · Page 3Linked to original sources
PubMed1998

The effects of excretions/secretions of Ostertagia circumcincta on ovine abomasal tissues in vitro.

Products excreted/secreted by Ostertagia circumcincta stimulated the in vitro release of pepsinogen from intact abomasal mucosal sheets and caused the contraction of strips of abomasal smooth muscle, also in vitro. However, responses occurred only when tissues had been derived from animals that were assumed to have experienced prior exposure to the parasite. The overall median responses for pepsinogen secretion in response to ES, expressed as the ratio of stimulated secretion to basal secretion, were 1.8 for previously exposed animals and 0.9 for parasite-naive animals. For the smooth muscle from the previously exposed animals, the overall median response to ES, expressed as a percentage of the maximal response to carbachol in the same tissues, was 27.0. No responses were seen in muscle from any parasite-naive animal. These results suggest that the responses obtained were hypersensitivity reactions to antigens released by the worms during in vitro culture, and occurring in tissues from animals sensitised by exposure to O. circumcincta in the natural environment.

Abomasum↗
PubMed1998

Infection of sheep with adult and larval Ostertagia circumcincta: abomasal morphology.

The infection of parasite-naive sheep with approximately 15,000 adult Ostertagia circumcincta via abomasal cannulae resulted in marked changes in the structure and function of the abomasum. The functional changes, which have been characterised previously, included elevated abomasal pH and increased serum concentrations of pepsinogen and gastrin. Eight days after the transplant of adult worms, the abomasa of recipient animals were significantly heavier than those of controls (P < 0.001), the thickness of the fundic mucosa was greater (P < 0.01), there were fewer parietal cells (P < 0.01) and increases in the numbers of mitotic figures and mucus-producing cells. Mucous cell hyperplasia was also evident in the fundic mucosae of sheep receiving a trickle infection of infective, third-stage O. circumcincta larvae and was prominent within nodules associated with larval development. In non-nodular mucosa, there was hyperplasia of mucous cells and changes in the distribution of parietal cells. Decreases in the number of parietal cells at the gland base were offset by increases at a mid-gland level, probably due to chronic hypergastrinaemia, so that, overall, total parietal cell number was unaffected. Mucous cell hyperplasia and the diminution of parietal cell number are seen in a diverse range of disease states and may be mediated by host growth factors such as Transforming growth factor-alpha. Alternatively, the cellular and/or the secretory changes in response to the presence of adult worms are mediated by chemicals that are cytotoxic/inhibitory for parietal cells, and released by the parasites themselves.

Abomasum↗
PubMed1998

Infection of sheep with adult and larval Ostertagia circumcincta: gastrin.

Gastric endocrine cell populations and serum and tissue gastrin have been examined in sheep which were infected either intraruminally by tube with 150,000 Ostertagia circumcincta larvae followed by a trickle infection of 10,000 larvae thrice weekly for 8 weeks or by the transfer of 15,000 adult worms directly into the abomasum and killed 8 days later. Depletion of both antral gastrin and somatostatin was evident in both groups: tissue gastrin concentrations were reduced by 85% in the trickle infection and both G cells (gastrin-containing) and D cells (somatostatin-containing) were pale and fewer after adult worm transfer. The concurrent depletion of antral gastrin and somatostatin supports the contention that the hypergastrinaemia in parasitised sheep is largely secondary to the increase in abomasal pH. Although there was no change in the proportions of G34 and G17 in the tissues, there was an increase in the longer form of gastrin in the circulation of the larval-infected sheep, suggesting that there may be differential secretion of G17 and G34 which may be exaggerated as the rate of secretion increases. Although the fundic mucosa was thicker following trickle infection, there was no evidence of enterochromaffin-like cell hyperplasia in either infected group. It is suggested that hyper-gastrinaemia may be beneficial to the host, as it may allow the abomasum to regain the ability to acidify its contents during continued exposure to the parasites.

Abomasum↗
PubMed1998

Changes in the zymogenic cell populations of the abomasa of sheep infected with Haemonchus contortus.

The effects of dietary urea supplementation and of a 10-week trickle infection regime, simulating chronic exposure to Haemonchus contortus, on the zymogenic population of the abomasa of Hampshire Down lambs was examined. At necropsy a variety of parameters including plasma pepsinogen concentration, the wet weights of abomasal fundic mucosal pieces and the amounts of pepsinogen contained in them, were assessed. Tissue pepsinogen concentration was measured as the total, acid-stable proteolytic activity present in mucosal homogenates, as well as immunohistochemically. The immunohistochemical findings were quantified using computer-aided image analysis. Elevation of plasma pepsinogen concentrations in infected animals was of borderline significance (P = 0.06). The fundic mucosae of infected animals were heavier (P < 0.02) than those of control animals, but there was no overall change in the pepsinogen content of tissues. Immunohistochemistry revealed that infected animals had increased numbers of zymogenic cells, due to mucous cell hyperplasia and the adaptation of cells to produce both mucins and pepsinogen. The pepsinogen content of chief cells, the major source of pepsinogen in uninfected animals, was reduced in infected lambs. Image analysis confirmed that at a mid-point of the mucosa of infected animals there was increased pepsinogen-specific immunoreactivity that corresponded with areas of mucosal hyperplasia. Mucous cell hyperplasia might therefore allow the maintenance of pepsinogen secretion in infected animals even if chief cell output is reduced.

Abomasum↗
PubMed1997

Measurement of cytotoxic T lymphocyte precursor frequencies reveals cryptic HLA class I mismatches in the context of unrelated donor bone marrow transplantation.

BACKGROUND: In this large, two-center study, 260 cytotoxic T lymphocyte precursor (CTLp) frequency assays, performed to assess patient-donor compatibility, were analyzed in relation to the degree of HLA matching. METHODS: While the tissue-typing techniques used at the Royal Postgraduate Medical School (RPMS) and Anthony Nolan Bone Marrow Trust (ANBMT) differ, the results of the analyses on the two sites are analogous, with high CTLp frequencies (>1:100,000) in 42% and 41% of recipient-donor pairs, respectively. RESULTS: Recipient-donor combinations with class I mismatches and class II identity were associated with high CTLp frequencies (collectively 83% vs. 17% low CTLp). This correlation was not as strong in pairs where class II mismatches were demonstrated (61% high vs. 39% low). Despite using different matching procedures, the RPMS and ANBMT both show that 32% of the "perfectly" matched pairs (i.e., where no mismatch was detected by any of the techniques used here) had high frequencies of recipient-specific CTLp. CONCLUSIONS: The failure of conventional methods to identify such a level of histoincompatibilities indicates that the CTLp assay has an important role in the selection of unrelated donors for bone marrow transplantation.

Bone Marrow Transplantation↗
PubMed1997

Physical and sexual abuse of children in the West Midlands.

OBJECTIVE: To describe the convicted and cautioned abusers and the nature of the physical and sexual abuse of children using a legal classification in an attempt to formulate operational criteria for future comparative studies. DESIGN: A retrospective sequential survey of all cautioned and convicted physical and sexual abusers between the January 1, 1988 and June 30, 1994. SETTING: The West Midlands police jurisdiction. SUBJECTS: 1,113 abused children and 964 abusers. RESULTS: The majority of all abuse involved a single child. Many abusers lived in the same household and were in a position of trust or quasi-trust. When strangers committed abuse, the majority of abuse was sexual. A third of the abusers were unemployed. Multiple abuse tended to be sexual and was perpetrated by men. The physical abuse of young children tended to be committed by younger women. No women over the age of 40 had sexually abused a child. Of the children under 12 months, 1.5% had been sexually abused and 8.5% had been physically abused. The greater proportion of physical abuse had occurred in children under 9 years of age whereas sexual abuse was perpetrated more often in girls aged 9 to 11 years. No girls were murdered in this survey. Significantly more boys had been buggered. CONCLUSION: This preliminary study is representative of all the cautioned and convicted cases within the selected 5-year period and obtained from a source of material hitherto unavailable. Many of the findings of this preliminary study are in line with previous studies. Substantial descriptive information has been obtained on a selected population of cautioned or convicted abusers. Further studies may indicate that the cautioned and convicted are more representative of abusers generally than previously thought. Expanded studies may eventually produce particularized profiles of both abusers and the abused, but even the limited guidance provided by this preliminary study will give some assistance to law enforcement agencies in detection and child protection agencies in identifying children at risk and targeting resources more efficiently.

Adolescent↗
PubMed1997

Molecular histocompatibility typing in unrelated donor bone marrow transplantation.

Increasing numbers of bone-marrow transplants are being performed with marrow from unrelated donors. There is clear evidence that genetic disparity is a major cause of graft-versus-host disease. However, until very recently, typing methods did not have sufficient resolution to identify the majority of histocompatibility alleles. DNA-based typing methods have the potential to define alleles unequivocally, and this will help in the selection of better matched marrow donors. Also, a number of studies have indicated that patient and donor pairs that had previously been identified as matched can frequently be shown to have been mismatched at one or more locus. Consequently, it may become more difficult in future to find completely matched donors. There is also evidence that some genetic mismatching may not be deleterious to the patient and it may now be possible to analyse the histocompatibility data with greater confidence and identify those mismatches that are tolerated. This will allow a larger number of transplants to be performed using unrelated donors.

Animals↗
PubMed1997

Factors influencing the outcome of bone marrow transplants using unrelated donors.

The use of unrelated donors for bone marrow transplantation (BMT) is associated with an increased morbidity and mortality when compared with HLA-identical donors, primarily due to an increased rate of graft-versus-host disease, but also to increased susceptibility to infections and graft failure. HLA matching for donors and recipients is the single most important factor influencing the outcome of BMT. However, unrelated donor selection generally relies on matching only for HLA-A, -B and -DR antigens without considering potential incompatibility for other HLA loci, such as HLA-C, -DQ and -DP. In addition, other factors that affect the outcome of BMT need to be taken into consideration in selecting the best unrelated donor. In this review, we will focus on the effects of HLA-associated factors in determining the result of a transplant procedure. We will also mention other relevant factors, drawing on our experience of laboratory studies performed at The Anthony Nolan Research Institute and clinical studies at the Hammersmith Hospital in London.

Bone Marrow Transplantation↗
PubMed1995

Different mechanisms of hydroxylation site selection by liver and kidney cytochrome P450 species (CYP27 and CYP24) involved in vitamin D metabolism.

A series of homologated 1 alpha-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 molecules with one to three extra carbons in the side chain were used to examine the substrate preferences and hydroxylation site selection mechanisms of the liver vitamin D3-25-hydroxylase (CYP27) and the target cell 25-hydroxyvitamin D3-24-hydroxylase (CYP24). Cultured and transfected cell models, used as sources of these hydroxylases, gave 23-, 24-, 25-, and 27-hydroxylated metabolites which were identified by their high performance liquid chromatography and GC-MS characteristics. Lengthening the side chain is tolerated by each cytochrome P450 isoform such that 25-hydroxylation or 24-hydroxylation continues to occur at the same rate as in the native side chain, while the site of hydroxylation remains the same for the liver enzyme in that CYP27 continues to hydroxylate at C-25 and C-27 (minor) despite the two-carbon-atom extension. Somewhat surprising is the finding that C-24 and C-23 (minor) hydroxylations also do not change as the side chain is extended by as much as three carbons. We conclude that CYP24 must be directed to its hydroxylation site(s) by the distance of carbon 24 from the vitamin D ring structure and not as in CYP27 by the distance of the hydroxylation site from the end of the side chain.

Calcitriol↗
PubMed1995

Comparison of four methods for the determination of plasma pepsinogen concentration.

Four methods for estimating plasma pepsinogen concentrations were compared to determine the most suitable for routine use. Three of the methods were colorimetric assays which used glycine-buffered albumin, albumin, or haemoglobin as their substrates. The fourth method was a radial diffusion assay which used casein in agarose as its substrate. All four methods gave reproducible results when replicates were assayed on the same day. However, the first method had the least day-to-day variation and was the only method which gave a linear relationship with different concentrations of pepsinogen in a plasma pool.

Albumins↗