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Biomedical subjects

P Baird

Publications and source records attributed to P Baird.

At least 19 recordsLinked to original sources
PubMed2002

Nerve growth factor expression and innervation of the painful intervertebral disc.

Following a previous description of nociceptive nerve fibre growth into usually aneural inner parts of painful intervertebral disc (IVD), this study has investigated whether nociceptive nerve ingrowth into painful IVD is stimulated by local production of neurotrophins. Immunohistochemistry and in situ hybridization have been used to investigate expression of the candidate neurotrophin, nerve growth factor (NGF), and its high- and low-affinity receptors trk-A and p75, respectively, in painful IVD excised for the management of low back pain. IVD from patients with back pain were of two types: those that when examined by discography reproduced the patient symptoms (pain level IVD) and those that did not (non-pain level IVD). Microvascular blood vessels accompanied nerve fibres growing into pain level IVD and these expressed NGF. The adjacent nerves expressed the high-affinity NGF receptor trk-A. These vessels entered the normally avascular IVD through the discal end plates. NGF expression was not identified in non-pain level or control IVD. Some non-pain level IVD had vessels within them, which entered through the annulus fibrosus. These did not express NGF nor did nerves accompany them. These findings show that nociceptive nerve ingrowth into painful IVD is causally linked with NGF production by blood vessels growing into the IVD, from adjacent vertebral bodies.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Expression of chondrocyte markers by cells of normal and degenerate intervertebral discs.

AIMS: To investigate the phenotype of cells in normal and degenerate intervertebral discs by studying the expression of molecules characteristic of chondrocytes in situ. METHODS: Human intervertebral discs taken at surgery were graded histologically, and classified on this basis as normal or degenerate. Eighteen of each type were selected, and in situ hybridisation was performed for the chondrocytic markers Sox9 and collagen II using (35)S labelled cDNA probes. Aggrecan was located by immunohistochemistry, using the monoclonal antibody HAG7E1, and visualised with an avidin-biotin peroxidase system. RESULTS: In the normal discs, strong signals for Sox9 and collagen II mRNA, and strong staining for the aggrecan protein were seen for the cells of the nucleus pulposus (NP), but reactions were weak or absent over the cells of the annulus fibrosus (AF). In degenerate discs, the Sox9 and collagen II mRNA signals remained visible over the cells of the NP and were again absent in the AF. Aggrecan staining was not visible in the NP cells, and was again absent in the AF. CONCLUSIONS: Cells of the normal NP showed expression of all three markers, clearly indicating a chondrocytic phenotype. In degeneration, there was evidence of a loss of aggrecan synthesis, which may contribute to the pathogenesis of disc degeneration. AF cells showed no evidence of a chondrocytic phenotype in either normal or degenerate discs.

Adult↗
PubMed2001

The Human Genome Project, genetics and health.

Three main reasons why a genetic approach is unlikely to be a solution to common diseases in the foreseeable future are discussed. The first is the great importance of environmental circumstances in determining health, the second reason is the great complexity of gene/gene, gene/environment interactions, and the third reason is human behavior with regard to compliance with medical recommendations. Since particular interests are likely to push for a genetic approach to disease, there will be a need to protect the public interest so that premature and inappropriate use of genetics is not made, and so that a balanced opportunity to better the health of all is not missed.

Environment↗
PubMed2000

Expression of parathyroid hormone-related protein and its receptor in bone metastases from prostate cancer.

Studies of breast cancer suggest that parathyroid hormone-related protein (PTHrP) is important in the development of bone metastases. To determine whether PTHrP expression is important in prostate cancer metastasis, immunohistochemistry and in situ hybridization were used to assess the expression of PTHrP and its receptor in primary prostate cancer and bone metastases from both prostate and non-prostate cancers. PTHrP was expressed in more prostate primary tumours than bone metastases (p=0.003, Fisher's exact test). All bone metastases from non-prostate cancers expressed PTHrP. In contrast, PTHrP receptor was expressed in all bone metastases, but in only 19% of primary prostate tumours (p=0.001). The receptor to PTHrP was found to be highly expressed in bone metastases from prostate and other primaries, whereas PTHrP protein was found to have lower expression in the bone metastases than in the primary tumours. In conclusion, the expression of the receptor to PTHrP is increased in bone metastases from prostate cancer and may play an important role in their formation.

Bone Neoplasms↗
PubMed1999

Effect of ovarian steroid deficiency on oestrogen receptor alpha expression in bone.

The mechanism by which oestrogen and hormone replacement therapy (HRT) maintain bone mass in women is still unclear. It has previously been shown that cells of osteoblast lineage in vivo, particularly osteocytes, express oestrogen receptor alpha (ERalpha). Nevertheless, it is still debatable whether oestrogen and the ovarian steroids have a direct affect on osteocytes. If they could regulate osteocyte ERalpha expression, this would be strong evidence for the involvement of these cells in the hormonal regulation of bone mass. This study therefore aimed to compare bone biopsies from women who were replete with ovarian steroids (pre-ovariectomy or post-HRT) with those from the same women when hormone-deficient (post-ovariectomy or pre-HRT) for cellular localization of ERalpha protein or mRNA expression by indirect immunofluorescence, or by in situ hybridization combined with reverse transcriptase-polymerase chain reaction (IS-RT-PCR) respectively. Image analysis showed that proportions of osteocytes positive for immunodetectable ERalpha were higher in hormone-replete than in hormone-deficient women (25+/-SEM 3 per cent, 12+/-SEM 4 per cent, respectively; n=5), with similar but non-statistically significant changes in osteoblasts. This was observed even when HRT was commenced 18 years after menopause. In contrast, grain volume/unit cell area of osteoblast mRNA signal was markedly higher when hormone-deficient (0.055+/-0.01) than when hormone-replete (0.016+/-0.004), with similar but non-significant differences in osteocytes. This preliminary study indicates up-regulation of osteocyte ERalpha protein by ovarian steroids in these patients, which is accompanied by decreased osteoblast ERalpha mRNA expression, providing further evidence for the involvement of osteocytes in the regulation of skeletal structure by ovarian steroids.

Bone and Bones↗
PubMed1999

Imaging of the rotator cuff and biceps tendon.

Several different imaging techniques are available for evaluating the rotator cuff and biceps tendon. The common disorders of impingement, rotator cuff tears and biceps tendonitis are discussed along with the role which the various imaging modalities can play in establishing their diagnosis. Plain radiographs can be helpful particularly with a history of trauma but give limited information on the soft tissues. Ultrasound is a useful and inexpensive means of assessing the rotator cuff and biceps tendon but has a number of limitations and varying reports on its accuracy. Computed tomography (CT) is most helpful in the evaluation of shoulder trauma but gives limited information on the soft tissues. Magnetic resonance imaging (MRI) is an accurate imaging modality for evaluating the rotator cuff and biceps tendon, allowing visualisation of the soft tissues and the adjacent bony structures.

Arm Injuries↗
PubMed1998

Localisation and semiquantitative assessment of hepatic procollagen mRNA in primary biliary cirrhosis.

BACKGROUND: Chronic liver disease is characterised by excessive deposition of collagen and other extracellular matrix proteins, produced mainly, but not exclusively, by activated hepatic stellate cells in the perisinusoidal space. In primary biliary cirrhosis (PBC) fibrosis is concentrated mainly around the portal tracts. AIMS: To examine the hypothesis that, in addition to hepatic stellate cells, portal tract fibroblasts might play a significant role in the deposition of collagen in PBC. METHODS: Fifty liver biopsy specimens from patients with PBC were studied. An in situ hybridisation technique was adapted to localise and measure semiquantitatively type I procollagen mRNA in formalin fixed, paraffin wax embedded sections, using an 35S labelled cRNA probe specific for the alpha 1 chain of rat type I procollagen. Hepatic fibrogenic activity was also assessed using serum type III procollagen peptide (PIIINP). RESULTS: In PBC, type I procollagen gene expression was significantly increased. Signal was localised mainly in and around inflamed portal tracts, to cells which had the appearances of portal fibroblasts. Signal activity in these cells correlated with the degree of portal fibrosis and inflammation and also with serum PIIINP concentrations. CONCLUSIONS: Results are consistent with the hypothesis that the excessive extracellular matrix, deposited within the liver in PBC, is synthesised not only by hepatic stellate cells but also by portal tract fibroblasts. The semiquantitative assessment of procollagen mRNA in liver biopsy specimens may provide a useful method of evaluating the rate of synthesis of collagen and therefore disease activity in patients with PBC.

Biomarkers↗
PubMed1997

Demonstration of estrogen receptor mRNA in bone using in situ reverse-transcriptase polymerase chain reaction.

Falling estrogen levels affect the female skeleton profoundly. Following menopause, estrogen lack is a major cause of osteoporosis. The site of estrogen action in human bone, however, is unclear, but responsive cells must express the estrogen receptor (ER). One obstacle to localizing these cells is that mRNA for ER is expressed in low copy number. Hence, conventional molecular techniques are either too insensitive to detect receptor transcripts (in situ hybridization) or necessitate amplification of RNA extracted from tissue [Northern analysis and polymerase chain reaction (PCR)], thus failing to identify the specific target cells within the mixed-cell population of bone. In situ PCR (IS-PCR) is a technique that combines the sensitivity of PCR with the localization of conventional in situ hybridization. The technique has previously been used primarily to detect single-copy genes and viral DNA within cells. More recently, incorporation of a reverse-transcriptase reaction (IS-RT-PCR) has allowed the technique to be used to identify rare mRNAs within tissues. We have therefore applied the technique of IS-RT-PCR to localize ER mRNA first in human breast tumors, a known positive tissue, and then in bone. Using conventional riboprobe in situ hybridization, ER transcripts were not detectable in any bone cells within sections taken from normal bone and several actively remodeling bone tissues, namely, Paget's disease, renal hyperparathyroidism, and healing fracture callus. The technique of IS-RT-PCR, however, allowed amplification of transcripts to a detectable level. Following two cycles of amplification, hybridization signal was observed in osteoblasts and to a lower level in osteoclasts and occasional osteocytes. This positive signal was more obvious after five cycles, particularly in osteoclasts and osteocytes. After ten cycles, although signal was increased in osteoclasts and osteocytes, it appeared to be decreased in osteoblasts, suggesting that overamplification leads to loss of target complex from these cells. We conclude that several cell types in human bone express ER mRNA in vivo.

Bone Marrow↗
PubMed1995

Canine bone marrow cell cultures infected with canine distemper virus: an in vitro model of Paget's disease.

We have previously shown that the canine paramyxovirus, canine distemper virus (CDV), is a possible aetiologic agent in Paget's disease of bone and in the canine bone disorder, metaphyseal osteopathy. More recently, we have examined the effects of CDV on the formation of multinucleated, tartrate resistant acid phosphatase positive, calcitonin receptor positive, osteoclast-like cells in cultures of canine bone marrow mononuclear cells, and shown that both in vitro and in vivo infection with CDV produced a dose dependent increase in the number and size of osteoclast-like cells. We have now extended these results to show that CDV infection induces interleukin-6 and c-Fos mRNA in these cells, similar to our recent findings in pagetic bone cells. These results further support the hypothesis that CDV might be involved in the aetiopathogenesis of Paget's disease and metaphyseal osteopathy and suggest that canine marrow culture systems will prove useful as an in vitro model to examine the disease processes in more detail.

Animals↗