Biomedical subjects

P J Ryan

Publications and source records attributed to P J Ryan.

At least 19 recordsLinked to original sources

PubMed1999

Identification and cloning of a connective tissue growth factor-like cDNA from human osteoblasts encoding a novel regulator of osteoblast functions.

We have identified and cloned a novel connective tissue growth factor-like (CTGF-L) cDNA from primary human osteoblast cells encoding a 250-amino acid single chain polypeptide. Murine CTGF-L cDNA, encoding a polypeptide of 251 amino acids, was obtained from a murine lung cDNA library. CTGF-L protein bears significant identity ( approximately 60%) to the CCN (CTGF, Cef10/Cyr61, Nov) family of proteins. CTGF-L is composed of three distinct domains, an insulin-like growth factor binding domain, a von Willebrand Factor type C motif, and a thrombospondin type I repeat. However, unlike CTGF, CTGF-L lacks the C-terminal domain implicated in dimerization and heparin binding. CTGF-L mRNA ( approximately 1.3 kilobases) is expressed in primary human osteoblasts, fibroblasts, ovary, testes, and heart, and a approximately 26-kDa protein is secreted from primary human osteoblasts and fibroblasts. In situ hybridization indicates high expression in osteoblasts forming bone, discrete alkaline phosphatase positive bone marrow cells, and chondrocytes. Specific binding of 125I-labeled insulin-like growth factors to CTGF-L was demonstrated by ligand Western blotting and cross-linking experiments. Recombinant human CTGF-L promotes the adhesion of osteoblast cells and inhibits the binding of fibrinogen to integrin receptors. In addition, recombinant human CTGF-L inhibits osteocalcin production in rat osteoblast-like Ros 17/2.8 cells. Taken together, these results suggest that CTGF-L may play an important role in modulating bone turnover.

Amino Acid Sequence↗

PubMed1998

Identification of phosphorylated proteins associated with the fibroblast growth factor receptor type I during early Xenopus development.

Signaling through the FGF receptor (FGFR) is required for mesoderm induction in Xenopus. Some of the downstream signaling molecules implicated in this developmental process include Ras, Raf and MAP kinase. In a previous report, we demonstrated that PLC gamma 1, Grb-2, SOS and Nck were associated with activated FGFR1s in a signaling complex in Xenopus blastulae. In addition, several unidentified phosphotyrosylproteins were present in the FGFR1 complex. Here we identify three of these proteins as Ras-GAP, the p85 of P13'K and SHP2, while demonstrating that c-Src and She were not associated with the FGFR1. Furthermore, we show that three additional phosphotyrosylproteins from the FGFR1 complex specifically bound to the adaptor molecule Nck.

Animals↗

PubMed1998

Orthopaedic manifestations of systemic disease.

Nuclear medicine studies can be initiated to detect or evaluate systemic diseases such as inflammatory arthritis or Paget's disease. This is usually because of the strengths of nuclear medicine studies such as high sensitivity, an ability to easily image the whole body, and typical diagnostic patterns of abnormalities. In other instances, a systemic disease may be incidentally suggested by a scintigram such as osteoporosis or hyperparathyroidism; or a focal abnormality such as a vascular necrosis may be detected that should indicate a systemic condition should be sought. Although most nuclear medicine studies have high sensitivity for disease, specificity is often less and, for a particular scan abnormality, several conditions may have to be considered. Familiarity with the varying patterns of abnormality associated with different disease is therefore vital to correct assessment.

Arthritis↗

PubMed1998

The impact of influenza and influenza-like illness on productivity and healthcare resource utilization in a working population.

Four hundred and eleven subjects who either reported to Occupational Health at onset of influenza or influenza-like illness (I/ILI) symptoms or on return to work completed questionnaires on entry to the study and after 28 days. On average they were incapacitated or confined to bed for 2.4 days, missing 2.8 days from work per episode of illness. On return to work, they reported reduced effectiveness and inability to resume normal activity until a mean 3.5 days after the onset of symptoms. Each participant reported a mean of 6.5 I/ILI symptoms. There was a positive correlation between the number of symptoms and bed days (r = 0.24) and missed work days (r = 0.18). There was a positive correlation between the number of healthcare contact and the number of reported symptoms (r = 0.23). A relatively high level of contact with general practitioners and pharmacists was observed and there was substantial use of both prescription and over-the-counter medication. In conclusion, the impact of I/ILI on productivity in a working population and the resultant cost to employers and employees may be considerable.

Adult↗

PubMed1998

A prospective comparison of clinical examination, MRI, bone SPECT, and arthroscopy to detect meniscal tears.

Recent studies have shown that SPECT bone scintigraphy is valuable to detect meniscal tears of the knee. This has not been formally assessed in a prospective study, and no substantive study has compared bone SPECT with other noninvasive diagnostic methods. One hundred consecutive patients referred to an orthopedic surgeon with undiagnosed knee pain were assessed by clinical examination, MRI, SPECT bone scintigraphy, and arthroscopy. The MRI and SPECT bone scan findings were reported blinded to other information. Using arthroscopy as a gold standard, both MRI and SPECT showed high diagnostic ability to detect meniscal tears, with respective sensitivity rate, specificity rates, and positive and negative predictive accuracies of 80%, 71%, 84%, and 71% for MRI and 84%, 80%, 88%, and 76% for SPECT. Some meniscal tears were detected by MRI alone (n = 5) or SPECT alone (n = 8). SPECT bone scintigraphy is a suitable alternative to MRI to detect meniscal tears. The comparable diagnostic ability of SPECT bone scintigraphy implies that it can be used successfully when MRI is unavailable or unsuitable.

Adult↗

PubMed1997

cDNA cloning of a novel, developmentally regulated immediate early gene activated by fibroblast growth factor and encoding a nuclear protein.

We have utilized the polymerase chain reaction (PCR)-based differential display methodology (Liang, P., and Pardee, A. B. (1992) Science 257, 967-969) to identify a novel transcript whose expression levels increased in Xenopus embryo explants during mesoderm induction by fibroblast growth factor. The PCR product was used to clone a 2.3-kilobase pair cDNA representing this transcript, which we have named er1 (early response 1). The er1 cDNA contained a single open reading frame predicted to encode a protein of 493 amino acid residues. A data base homology search revealed that the predicted ER1 amino acid sequence contains three regions of similarity to the rat and human proteins encoded by the metastasis-associated gene, mta1, and two regions of similarity to the Caenorhabditis elegans sequence that is similar to mta1. The fibroblast growth factor-induced increase in er1 steady-state levels was not dependent on de novo protein synthesis, demonstrating that er1 is an immediate-early gene. Northern blot analysis revealed a single 2.8-kilobase pair mRNA that was observed predominantly during the initial cleavage and blastula stages of Xenopus development, with little or no detectable mRNA during subsequent development. Quantitative PCR analysis of early developmental stages showed that er1 peaked during late blastula. Computer-assisted analysis of the predicted ER1 amino acid sequence revealed two putative nuclear localization signals, four highly acidic regions clustered at the N terminus and a proline-rich region located near the C terminus. Subcellular localization by immunocytochemistry revealed that the ER1 protein was targeted exclusively to the nucleus. Transactivation assays using various regions of ER1 fused to the DNA binding domain of GAL4 demonstrated that the N-terminal acidic region is a potent transactivator. These data suggest that ER1 may function as a transcription factor.

3T3 Cells↗

PubMed1997

Overview of role of BMD measurements in managing osteoporosis.

The advent of effective treatments and the opportunity to precisely and accurately measure bone mass have probably been the greatest advances in the field of osteoporosis in the last decade. Bone densitometry has become the most widespread noninvasive method for the detection of osteoporosis and to provide advice on risk of future fractures. It has achieved an unquestioned role in clinical decision making for the management of osteoporotic patients.

Age Factors↗

PubMed1997

Bone scintigraphy in metabolic bone disease.

The bone scan has well-recognized appearances in metabolic bone diseases, with its main clinical value found in focal conditions or the focal complications of disease. In clinical practice, the bone scan is most widely used to detect fractures in osteoporosis and pseudofractures in osteomalacia and to evaluate Paget's disease.

Bone Diseases, Metabolic↗

PubMed1997

The prevention of early postmenopausal bone loss by cyclical etidronate therapy: a 2-year, double-blind, placebo-controlled study.

PURPOSE: To determine whether intermittent cyclical etidronate therapy can prevent early postmenopausal bone loss. PATIENTS AND METHOD: This was a 2-year outpatient, randomized, double-blind, placebo-controlled clinical trial. The subjects were 152 women within 1 to 10 years of the onset of menopause and bone mineral density (BMD) between 0 and -2 SD of normal values for a 50 year old woman. The women were stratified according to years since the menopause (1 to 3 years: n = 43; 4 to 6 years: n = 53; 7 to 10 years: n = 56). Measurements of lumbar spine, proximal femur and total body BMD were performed at baseline, 12 and 24 months by dual x-ray absorptiometry. Biochemical markers of bone resorption and bone formation were measured on the same visits. RESULTS: One hundred thirty-five subjects completed the study. Mean percentage change in lumbar spine BMD (and SEM) at 2 years was +2.14 (0.47)% in the etidronate group and -1.72 (0.41)% in the placebo group. Results for lumbar spine BMD in the treated and control groups stratified according to years since the menopause were: 1 to 3 years: +1.73 (0.84)% and -3.30 (0.70)%; 4 to 6 years: +1.37 (0.88)% and -1.80 (0.61)%; 7 to 10 years: +3.42 (0.61)% and -0.38 (0.70)%. The effect of both treatment group and menopausal stratum were highly statistically significant for lumbar spine and total body BMD. Treatment group, but not stratum, was significant for BMD in the proximal femur. Markers of bone resorption and bone formation were significantly decreased by etidronate therapy. CONCLUSIONS: Cyclical etidronate prevents bone loss in the total skeleton and at the clinically relevant sites (spine and proximal femur) even in the early postmenopausal years. Hence, it appears to be an effective and safe nonhormonal therapy in postmenopausal women with normal or low BMD.

Absorptiometry, Photon↗

PubMed1997

Distinction between pleural mesothelioma and pulmonary adenocarcinoma using MOC31 in an asbestos sprayer.

Asbestos exposure may cause asbestosis, pleural plaques and benign pleural disease, and may pre-dispose to malignant mesothelioma and other neoplasms. The occurrence to two primary tumours in the same patient is rare, and the appearance of a pleural mesothelioma and another lung tumour is exceptional. The present case report describes a patient who, by standard immunohistochemistry, was thought to have mesothelioma at pleuro-pneumonectomy, and adenocarcinoma in the other lung at post-mortem 5 months later. Subsequent investigation using the MOC31 antibody demonstrated a single pathology of adenocarcinoma of the lung. The additional use of this antibody has important histopathological and legal implications.

Adenocarcinoma↗

PubMed1997

Spinal bone SPECT in chronic symptomatic ankylosing spondylitis.

Bone SPECT has acquired a useful role in the evaluation of acute and chronic back pain. Spinal pain is also a characteristic of chronic ankylosing spondylitis. The authors investigated the bone SPECT appearances of the lower thoracic and lumbar spine in 28 symptomatic patients with established ankylosing spondylitis, half of whom had complete ankylosis of the sacroiliac and one third complete ankylosis of the intervertebral joints. SPECT abnormalities were identified in 89%. Facetal joint uptake was found in 16 (57%) patients, of whom 7 (25%) had three or more, and 2 (7%) had seven or more active sites. The only other common site of uptake was in the vertebral body, in which 15 patients (54%) showed increased uptake with three or more sites found in 3 (11%) patients. The authors conclude that SPECT abnormalities in the lower thoracic and lumbar spine are frequently found in patients with ankylosing spondylitis, with the most common sites of abnormality in the facetal joints or vertebral body. Multiple sites of uptake in the facetal joints maybe striking in such patients and has not been previously described.

Adult↗

PubMed1996

Measurement of the secretion of technetium-99m hexamethylpropylene amine oxime into breast milk.

There are no published data for the activity of technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) found in breast milk. The amount of radioactivity in breast milk following the administration of 500 MBq 99mTc-HMPAO for a brain perfusion study has been measured. The effective dose to the infant was calculated to be 0.26 mSv, so necessitating no interruption of breast feeding. Unbound 99mTc is readily secreted into breast milk and the effective dose will remain less than 1 mSv if the 99mTc-HMPAO labelling efficiency is >/=99% for the worse reported case, and could remain <1 mSv for the mean reported case for 99mTc-HMPAO labelling efficiencies down to 94%.

Brain↗

PubMed1996

Isotope imaging.

Patients with a wide variety of rheumatological conditions can be usefully investigated by nuclear medicine techniques and particularly by bone scintigraphy. This aspect of nuclear medicine work is increasing and the trend can be expected to continue. The principal conditions that can be imaged are sports medicine injuries, osteomyelitis, avascular necrosis, reflex sympathetic dystrophy syndrome, enthesopathies and bio-mechanical stress lesions, inflammatory arthropathies, metabolic bone disease and miscellaneous bone conditions such as costo-chondritis. Single photon emission tomography (SPECT) has provided new indications for bone scintigraphy such as the evaluation of spondylolysis and facet syndrome in the spine and of meniscal tears and ligamental lesions.

Arthritis↗

PubMed1996

The value of SPECT scans in identifying back pain likely to benefit from facet joint injection.

Lumbar facet disease is sometimes implicated in low back pain. Identification is difficult and this may account for a variable response. Single photon emission computerized tomography (SPECT) is a scanning technique which enables localization of facet joint pathology. We determined whether recognition of facet disease by this method improved the response to corticosteroid injection treatment. Fifty-eight patients with low back pain and displaying accepted clinical criteria for facet joint disease were evaluated by SPECT. Twenty-two had facetal uptake of isotope. These and the tender facet joints of 36 scan-negative patients were injected with 40 mg methylprednisolone and 1 ml 1% lignocaine under X-ray control. Pain was assessed by a blind observer using the McGill questionnaire (MGQ), Present Pain Intensity score (PPI) and a Visual Analogue Scale (VAS). VAS, PPI and MGQ were reduced in the scan-positive patients at 1 month (P = 0.05, P = 0.0005, P = 0.005) and MGQ at 3 months (P = 0.01), whilst scan-negative patients were unchanged. The percentage of scan-positive patients who reported improvement was 95% at 1 month and 79% at 3 months, significantly greater than the control group (P = 0.0005, P = 0.01). Within 6 months, pain improvement in the SPECT-positive group was no longer statistically significant. Tenderness did not correlate with increased uptake on SPECT scan. Osteoarthritis of the facets was more common in the SPECT-positive patients (P < 0.001), but did not correspond with sites of increased uptake on SPECT scan. These results suggest that SPECT can enhance the identification of back pain sufferers likely to obtain short-term benefit from facet joint injection.

Adolescent↗

PubMed1996

A comparison of MRI and bone SPET in the diagnosis of knee pathology.

Bone single photon emission tomography (SPET) of the knees has been shown to be of diagnostic value for the investigation of knee pain. This study compared bone SPET with magnetic resonance imaging (MRI) for the diagnosis of knee disorders. Thirty-six patients were studied with modalities, performed an average of 4 months apart (range 0-10 months). There was agreement on the presence or absence and nature of pathology in 24 (67%) patients. In a further three patients, there was an abnormal SPET with equivocal change for the same pathology on MRI. Equivocal change on both modalities for the same pathology were found in one patient. Three patients had abnormalities on MRI with normal SPET, with the remaining patients having equivocal or non-specific changes on one modality only. In the majority of patients, there was agreement on the presence or absence of pathology and the nature of pathology with both modalities. Significant pathology detected on MRI was also identified by bone SPET. This initial study suggests that further work should be undertaken to evaluate the role of bone SPET as a screening test for the evaluation of knee disorders and its role in relation to MRI is justified.

Adolescent↗

PubMed1996

Referral for lung transplantation: experience of a Birmingham Adult Cystic Fibrosis Centre between 1987 and 1994.

BACKGROUND: Whilst much is known of the outcome of lung transplantation for patients with cystic fibrosis, less is known about those patients who are either not referred for transplantation or who die before a donor is available. The referral practice and outcome of all the cystic fibrosis patients in one clinic was documented, whether or not they were assessed for lung transplantation. The results give a perspective on the impact of the current transplantation programmes on the adult cystic fibrosis population as a whole. METHODS: A retrospective study was made of patient deaths and referrals for lung transplantation between 1987 and 1994 from the Adult Cystic Fibrosis Clinic at Birmingham Heartlands Hospital. RESULTS: The Birmingham Heartlands Adult Cystic Fibrosis Clinic has managed 192 patients since its beginning and currently cares for 141 patients. Since 1987 there have been 16 deaths in patients with cystic fibrosis who were considered unsuitable for lung transplantation. Of 49 patients referred for lung transplantation, 47 were accepted on to a provisional or active waiting list. The mean (SE) age at referral was 23.9 (0.7) years and mean (SE) forced expiratory volume in one second (FEV1) was 0.87 (0.04) 1. Fourteen patients died whilst awaiting transplantation and 19 received donor lungs. There have been 10 deaths in the transplanted group. Survival following transplantation was 58% at one year and 52% at two years. CONCLUSION: Most of the deaths that occurred in the Cystic Fibrosis Clinic were in patients who either were not considered suitable for transplantation or were still awaiting transplantation. Whilst lung transplantation is the focus for many adults with cystic fibrosis, lack of donor organs has limited the impact of transplant programmes on the clinic.

Adolescent↗

PubMed1996

Co-existing conjunctival non-Hodgkin's lymphoma and pulmonary sarcoidosis.

A 55 year old woman with a conjunctival non-Hodgkin's lymphoma was found to have pulmonary nodules on a thoracic computed tomographic scan which were initially thought to be lymphomatous deposits. A subsequent biopsy specimen demonstrated granulomas consistent with sarcoidosis. The relationship between sarcoidosis and malignancy, in particular lymphoma, is discussed.

Conjunctival Neoplasms↗

PubMed1996

SPECT bone scintigraphy of anterior cruciate ligament injury.

UNLABELLED: This retrospective analysis of SPECT bone scans of the knee was undertaken to define typical bone scan appearances and to assess the sensitivity of this method. We looked at 14 patients, mostly with chronic knee pain, who had anterior cruciate ligament (ACL) tears detected by MRI. METHOD: Of the 14 patients, 10 were referred for bone scanning following injury and 4 complained of chronic knee pain without injury. Planar scans were performed 4 hr after the injection of 750 MBq of 99mTc-MDP. Tomographic images were obtained by a 64 x 20-sec acquisition over 360 degrees using a high-resolution collimator. MRI imaging included axial and sagittal, T1 weighted and coronal fast field echo (FFE) sequences. Ten patients also had arthroscopy performed. RESULTS: MRI scans showed 6 lone ACL tears and 8 combined with other ligamentous injuries. SPECT scans showed abnormalities in 10 patients in the region of ACL insertions but only 4 planar studies were abnormal. SPECT identified focal activity at the upper (n = 8) or lower (n = 2) insertion of the ACL. Six of 10 arthroscopies confirmed ACL tears, 2 complete and 4 partial. Overall, agreement was found with MRI in 10 of 14 cases and in 8 of 10 with arthroscopy. Abnormalities were identified in 10 of 11 regions of other ligament or bone injury identified by MRI. CONCLUSION: SPECT bone scanning of the knee is superior to planar imaging in detecting ACL injury and is a sensitive technique. Focal activity may be seen at either end of ACL attachment but more commonly at the upper femoral insertion. Knee SPECT may be a valuable examination in suspected ACL injury, particularly if MRI is not available, is equivocal or where clinical signs are absent.

Adult↗