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Biomedical subjects

C J Watson

Publications and source records attributed to C J Watson.

At least 109 records · Page 6Linked to original sources
PubMed1994

CD4 and CD8 monoclonal antibody therapy in canine renal allografts.

Therapy with CD4 and CD8 monoclonal antibodies was evaluated in dogs which received double-haplotype MHC-mismatched renal allografts. Neither CD4 nor CD8 monoclonal antibodies given alone prolonged allografts survival (creatinine > or = 300 micromol/l) beyond 7 days. However, combined therapy with CD4 and CD8 antibodies given up to day 10 did prolong allograft survival to a median of 14 days. A longer (21 day) course of CD4 and CD8 antibodies did not extend allograft survival further. The effect of prolonged antibody therapy was restricted by the occurrence of both an antiglobulin response and an anaphylactoid reaction to the monoclonal antibody preparation. When the CD4 and CD8 antibodies were combined with a pan-T-cell-depleting Thy-1 antibody, the survival of double-haplotype mismatched allografts was further prolonged (median 16 days). The median survival of single-haplotype mismatched renal allografts on this triple therapy was 21 days, with one surviving to day 36.

Anaphylaxis↗
PubMed1994

Regulation of the sheep beta-lactoglobulin gene by lactogenic hormones is mediated by a transcription factor that binds an interferon-gamma activation site-related element.

Polypeptide and steroid hormones regulate the transcription of milk protein genes in the mammary gland. The promoter sequence motifs and factors through which these hormones mediate their effects in vivo are not clearly defined. Milk protein binding factor (MPBF) is a factor that has recognition sites in the promoters of many milk protein genes including three sites in the promoter of the sheep beta-lactoglobulin (BLG) gene. Mutagenesis of these sites reduced expression of the BLG gene in lactating mammary glands of transgenic mice but did not affect the tissue specificity of the transgene. Furthermore, mutation of all three sites abolished the response of the BLG gene to lactogenic hormones in HC11 mammary cells. Together these results indicate that MPBF mediates the effects of lactogenic hormones in the mammary gland but does not play a role in determining mammary specificity. The similarity between the MPBF binding site and the gamma-interferon activating site suggests that MPBF is related to the STAT family of cytokine-induced transcription factors.

Animals↗
PubMed1993

Cis-urocanic acid stimulates human peripheral blood monocyte prostaglandin E2 production and suppresses indirectly tumor necrosis factor-alpha levels.

Photoisomerization of trans-urocanic acid (UCA) in the stratum corneum has been implicated in the immunosuppression detected after irradiation with UVB (UV wavelength of 280-320 nm). In this study, cis-urocanic acid suppressed human monocyte production of TNF-alpha by a PGE2-dependent mechanism. This contrasted with the mechanism involving histamine type 2 receptors by which the UCA structural analogue, histamine, suppressed monocyte TNF-alpha production. Histamine type 1 receptor antagonists were without effect on both the cis-UCA- and histamine-induced suppression of monocyte TNF-alpha levels. As indomethacin can reverse UVB-immunosuppression in murine models, we may have identified one of the cellular mechanisms responsible for reduced delayed-type hypersensitivity responses. Decreased TNF-alpha levels, by restricting further cytokine recruitment, may also limit the development of the inflammatory components of hypersensitivity responses.

Brompheniramine↗
PubMed1993

CD4 and CD8 monoclonal antibody therapy: strategies to prolong renal allograft survival in the dog.

The value of CD4 and CD8 monoclonal antibody therapy in tolerance induction has been demonstrated in rodent transplant models. In this paper the immunosuppressive potential of CD4 and CD8 monoclonal antibodies for dog renal allografts was evaluated as a preliminary to tolerogenic studies in this large animal model. Monoclonal antibodies were given for a maximum of 10 days after transplantation. Therapy was stopped prematurely following adverse reactions associated with the recipient developing an antibody response against the foreign (rat) therapeutic monoclonal antibody. Blood trough levels of CD4 and CD8 antibodies indicated that saturating doses were achieved. Although neither CD4 nor CD8 alone prolonged allograft survival (rejection by day 7), combination of CD4 and CD8 antibodies resulted in good graft function for a median of 14 days. The effect of removing circulating T lymphocytes was also assessed using a lytic Thy-1 monoclonal antibody. Alone Thy-1 had little effect but, when combined with CD4, the median allograft survival time was increased to 15.5 days. Reduction of the number of circulating T lymphocytes appears complementary to blockade of CD4 for immunosuppression, while blockade of CD4 combined with removal of CD8 also favours allograft survival.

Animals↗
PubMed1993

Stimulation of ecdysteroidogenesis by small prothoracicotropic hormone: role of cyclic AMP.

Prothoracicotropic hormones (PTTHs) stimulate synthesis and secretion of ecdysteroids by insect prothoracic glands. In Manduca sexta, PTTH exists as two size variants, small and big PTTH. Experiments were performed to assess the possible role of cyclic AMP in small PTTH signal transduction. cAMP analogs, or agents that increase intracellular cAMP, stimulated ecdysteroidogenesis. Small PTTH enhanced glandular cAMP levels; the rise in cAMP preceded an increase in ecdysteroid secretion. Prothoracic glands accumulated less cAMP when treated with small PTTH than when treated with big PTTH. A phosphodiesterase inhibitor (1-methyl-3-isobutylxanthine) (MIX) increased the amount of cAMP in glands treated with small but not big PTTH, suggesting that glandular phosphodiesterase activity may be elevated in the presence of small PTTH. PTTH-stimulated ecdysteroid secretion was suppressed by a cAMP antagonist (Rp-cAMPS). The effects of small and big PTTH on ecdysteroidogenesis were non-additive. The combined results suggest that cAMP is employed as a second messenger by both prothoracicotropins, and that there may be subtle differences in their respective mechanisms of action.

1-Methyl-3-isobutylxanthine↗
PubMed1993

A disease-associated germline deletion maps the type 2 neurofibromatosis (NF2) gene between the Ewing sarcoma region and the leukaemia inhibitory factor locus.

RFLP typing of members of a neurofibromatosis type 2 (NF2) family suggested that affected individuals were hemizygous at the neurofilament heavy chain (NEFH) locus, possibly as a result of a disease-associated deletion. Conventional karyotyping revealed no evidence for a deletion and all or a majority of the affected family members were heterozygous for closely linked markers which mapped proximal to the NEFH locus (D22S1 and D22S56) and for the distal marker D22S32. FISH analysis confirmed a disease-associated germinal deletion on 22q which encompassed the NEFH locus, which is known to be very closely linked to NF2, but did not extend as far as the proximal Ewing sarcoma region or the distal leukaemia factor (LIF) locus. PFGE analysis with a LIF cosmid subclone identified patient-specific NotI and MluI fragments and suggested that the deletion is about 700 kb in length. Although this large deletion could be expected to eliminate a considerable fraction, and possibly all of the NF2 gene, the resulting phenotype is the mild, so-called Gardner subtype of NF2. The deletion should provide a useful mapping resource for characterising the chromosomal region containing the NF2 locus.

Alleles↗
PubMed1993

A comparative study of cyclosporine and its derivative SDZ IMM-125 in canine renal allografts.

The immunosuppressive efficacy of CsA and its derivative SDZ IMM-125 was compared in highly mismatched mongrel dogs in receipt of renal allografts. At an equal dose of 15 mg/kg/day and in the same drug vehicle, SDZ IMM-125 was not superior to CsA in prolonging allograft survival. Whole blood levels of SDZ IMM-125 were lower than those achieved for CsA. No specific drug-related side effects were noticed in this model.

Animals↗
PubMed1993

Stress and strain distribution in the bone surrounding a new design of dental implant: a comparison with a threaded Branemark type implant.

The stress and strain distributions in the bone surrounding a new dental implant, designed specifically for use with a bioactive porous coating and thus having a fully bonded interface to the bone, have been analysed. The new implant geometry was slightly tapered, with deep concentric grooves to allow bone ingrowth and load transfer, and had a parallel cylindrical section at the neck. The results have been compared with stress and strain predictions in the bone surrounding a 'Branemark type' threaded implant with a fully bonded interface. Under axial loading both implant types produced similar stress and strain distributions with a higher level of stress in the cortical bone surrounding the neck of the implant. Under lateral loading a high stress concentration was found in the neck region of both implants, but this was lower around the neck of the new design compared with the threaded implant. When the new implant was surrounded by cancellous bone, the reduction in the stress concentration was up to 50 per cent. This reduction should help to reduce fatigue failure and bone resorption in this area under lateral loading.

Bone Density↗
PubMed1993

A statistical evaluation of mammography: crucial questions for health systems.

This article reviews data on incidence and mortality rates from breast cancer and provides the results from applications of Bayes' Theorem and a test of homogeneity to investigate the efficacy of mammographic screening for breast cancer. The results of our analyses indicate that the accuracy and effectiveness of mammographic screening for breast cancer are debatable. Consequently, we identify crucial unanswered questions for health systems about the heavy reliance on mammography. We recount the current recommendations, standards of practice, and utilization of mammography for breast cancer screening. Finally, we question the language used to describe the conclusions of these studies.

Adult↗
PubMed1992

A survey of complete denture prosthetics for the elderly, the handicapped and difficult patients.

A survey was carried out to establish information on the facilities and management of the elderly and the handicapped and to evaluate the treatment of the difficult edentulous patient in general dental practice. A postal questionnaire was sent to a total of 1090 dentists in three regions of England and Wales. There was a 50.4% response. Ninety-nine per cent of practitioners were able to treat the ambulant elderly, whereas only 72% offered treatment if the patient was wheelchair dependent. Ninety-six per cent of all respondents undertook domiciliary visits. All practitioners provided prosthetic treatment (complete and partial dentures) for the elderly, whereas fewer felt able to treat the physically and the mentally handicapped. There was less conservative and periodontal treatment provided than prosthetic treatment. A similar pattern was obtained in all three regions. Forty-seven per cent preferred to treat difficult complete denture patients privately, 44% under the NHS and 6% not at all. There were regional variations in the referral patterns of these difficult denture cases. The majority of respondents considered that there should be more opportunities for postgraduate education in prosthetic dentistry.

Aged↗
PubMed1992

Computed tomography in blunt abdominal trauma: an analysis of clinical management and radiological findings.

We have retrospectively assessed the computed tomography (CT) findings in 92 patients suffering severe blunt abdominal trauma. Surgical findings and clinical follow-up were correlated with the CT findings. In nine patients CT was first used after emergency surgery and provided baseline data which was useful for further management. In two patients CT did not demonstrate small hepatic lacerations seen during previous surgery. No deaths were recorded. In 16 patients surgery followed CT within 24 h; there was good correlation between the CT and operative findings in 10 patients. However, CT failed to detect significant solid organ injury in five patients and was misleading (false positive) in another patient. There were two deaths amongst these 16 patients. Sixty-seven haemodynamically stable patients were initially managed non-operatively. Fifteen of these 67 patients had normal CT examinations; only one had subsequent laparotomy (for reasons unconnected with the trauma) where no injury was detected; there were no deaths. Of the 52 patients with an abnormal CT examination, 43 were successfully managed non-operatively. There were three deaths, including one where an injury missed at CT contributed to the demise of the patient. After an initial trial of non-operative management, the remaining six patients went to surgery where there was good concordance with the CT findings except for one missed renal injury. Active non-operative management of blunt abdominal trauma is widely accepted in haemodynamically stable patients and this report shows how CT supports this policy of surgical restraint in such cases. However, on review CT missed 13 injuries in nine patients overall; stricter attention to technique and better equipment may lead to improved results in the future.

Abdominal Injuries↗
PubMed1992

Finite element stress and strain analysis of the bone surrounding a dental implant: effect of variations in bone modulus.

The long-term clinical performance of a dental implant is dependent upon the preservation of good quality bone surrounding the implant and a sound interface between the bone and the biomaterial. Good quality bone is itself dependent upon the appropriate level of bone remodelling necessary to maintain the bone density and the avoidance of bone microfracture and failure. Both processes are governed by the stress and strain distribution in the bone. In this study, a dental implant which had the same geometry as the Branemark system, but with a bioactive surface coating added to produce a direct bond to the bone, was analysed. A finite element stress and strain analysis has been carried out for a range of bone density distributions under axial and lateral loading. The predictions indicated that there was no evidence of strain shielding around the neck of the implant. With lateral loading, high values of von Mises stresses (18 M Pa) were predicted around the neck of the implant. A reduction in the elastic modulus of the bone around the neck of the implant by a factor of 16 only produced a twofold reduction in the peak stress. This resulted in stress levels capable of inducing fatigue failure in this much weaker bone. This analysis has demonstrated that it is extremely important to have good quality dense bone around the neck of the implant to withstand the predicted peak stresses of between 9 and 18 M Pa. Failure to achieve this after implantation and subsequent healing may result in local fatigue failure and resorption at the neck upon resumption of physiological loading.

Bone Density↗