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Biomedical subjects

A J Freemont

Publications and source records attributed to A J Freemont.

At least 19 recordsLinked to original sources
PubMed1995

Herniated intervertebral disc-associated periradicular fibrosis and vascular abnormalities occur without inflammatory cell infiltration.

STUDY DESIGN: Prospective histologic comparison of perineural tissues from patients requiring decompression surgery for herniated intervertebral disc with those from cadaveric controls. OBJECTIVES: To examine the significance of herniated intervertebral-disc-associated perineural vascular and fibrotic abnormalities with respect to back pain symptom generation. SUMMARY OF BACKGROUND DATA: Previous cadaveric studies have demonstrated perineural vascular congestion, dilatation, and thrombosis and perineural and intraneural fibrosis occurring in association with herniated intervertebral disc. It was suggested that these neural abnormalities were the result of ischemia, due to venous outflow obstruction, and also represented a possible cause of ongoing back pain symptoms. Criticisms of such a conclusion arose, however, because the possibility could not be excluded that these abnormalities were the result of postmortem artifact. METHODS: Histologic and immunohistochemical comparison of discal and peridiscal tissues removed from 11 patients with radiographically proven herniated intervertebral disc requiring decompressive surgery and from 6 fresh cadavers without history of back pain in life. RESULTS: Histology and immunohistochemistry of perineural and extraneural tissues from patients revealed vascular congestion, neovascularization, and endothelial abnormalities including luminal platelet adhesion, in association with reductions in von Willebrand factor levels, together with perivascular and perineural fibrosis. Elevated fibrogenic cytokine concentrations were also detected in patients' tissues. These changes occurred without evidence of inflammation and were absent in cadaveric control tissues. CONCLUSIONS: The vascular abnormalities detected in patients may represent an important etiopathologic factor predisposing to intraneural and perineural fibrosis, and hence to chronic pain symptoms, after disc herniation. It seems important to preserve the perineural microcirculation following disc herniation.

Adult↗
PubMed1995

Preliminary in situ identification of estrogen target cells in bone.

Although estrogens profoundly influence skeletal growth and maturation, their mechanism of action is still unclear. To identify their target cells in bone, estrogen receptors were located by immunofluorescence using the H222 monoclonal antibody in cryosections (both undecalcified and briefly decalcified) of hyperplastic mandibular condyle (persistent asymmetric mandibular growth) from a 14-year-old girl and radius and ulna from an 18-month-old female pig (epiphyseal fusion) and from a 3-month-old guinea pig (epiphyses open). Bone was removed from the animals at the peak of estrus. The most striking feature in all three species was the high proportion (approximately 50%) of receptor positive osteocytes. Although all sections contained active bone-forming surfaces, we were unable to identify clearly osteoblasts or lining cells that were estrogen receptor positive. In pig bone only, distinctive groups of receptor positive chondrocytes, with a pericellular localization of collagen type 1, were detected above the growth plate but below secondary centers of ossification. This observation suggests that osteocytes are major skeletal estrogen target cells and may be involved in coordinating the response of surface bone cells to the hormone, and further that chondrocytes may be involved in estrogen-induced epiphyseal growth plate fusion.

Adolescent↗
PubMed1995

Localization of pro-collagen type II mRNA and collagen type II in the healing tooth socket of the rat.

Sprague-Dawley rats (50 days old) were anaesthetized and the maxillary right molars extracted. The rats were killed at 2, 3, 6, 8 and 10 days after extraction. The maxillae were dissected and prepared for either routine histology, in situ hybridization for pro-collagen type II mRNA, or immunohistochemical detection of collagen type II. Pro-collagen type II mRNA was expressed maximally in the healing tooth socket at 8 days after the extractions, but the protein was not expressed at any time. This suggests that the translation of pro-collagen type II mRNA does not occur in osteoblasts following tooth extraction. Ossification was present in the socket at 6 days after the extractions, which is consistent with the suggestion that an early feature of osteoblastic differentiation may be the expression of type II pro-collagen mRNA.

Alveolar Process↗
PubMed1995

Platelet-derived growth factor expression in normally healing human fractures.

Platelet-derived growth factor (PDGF) has been shown to have effects on bone and cartilage cells in vitro, but its role in vivo in bone repair is not clear. We studied biopsy material from 16 normally healing fractures at a variety of times after injury, using immunohistochemistry for PDGF and in situ hybridization for PDGF A and B chains. PDGF A-chain gene was found to be expressed by many cell types over a prolonged period during fracture healing. These cells included endothelial and mesenchymal cells in granulation tissue and osteoblasts, chondrocytes, and osteoclasts later during fracture healing. PDGF B-chain gene expression was more restricted, being detected principally in osteoblasts at the stage of bone formation. PDGF was detected using immunohistochemistry in the cell types expressing PDGF A. These findings indicate that PDGF is expressed during normal human fracture repair, and the in vitro data also suggest that PDGF is likely to be an important local regulator in this process.

Biopsy↗
PubMed1995

Histomorphometric classification of postmenopausal osteoporosis: implications for the management of osteoporosis.

AIMS: To define and group static and dynamic iliac crest histomorphometric parameters in women with established osteoporosis. METHODS: Iliac crest biopsy specimens from 146 white women were sectioned undecalcified and examined using image analysis. RESULTS: Five distinct groups were defined on the basis of histomorphometric changes in cell function: group 1, decreased osteoblastic and osteoclastic activity; group 2, decreased osteoblastic and increased osteoclastic activity; group 3, increased osteoblastic and osteoclastic activity; group 4, no bone surface cell activity; and group 5, apparently normal osteoblastic and osteoclastic activity. CONCLUSIONS: Five distinct subgroups of patients with postmenopausal osteoporosis can be defined based on changes in bone cell function. Defining cellular dysfunction in this way may be important for tailoring treatment regimens to the needs of individual patients.

Age Factors↗
PubMed1994

Long-term follow-up of aplastic anaemia.

Of 61 patients with aplastic anaemia (AA) diagnosed in our hospitals, 37 survived more than 2 years; actuarial survival of this latter group was 58%, with a median follow-up of living patients of 10.2 years. Laboratory and clinical data pertaining to these long-term survivors was scrutinized to determine the incidence of clonal disorders, which was identified in 43%. Morphological evidence of the myelodysplastic syndrome (MDS) was found in 13 (35%), including four cases of RAEB; four (11%) developed PNH. Of 23 patients studied, four showed karyotypic abnormalities, but these did not always coincide with morphological features of MDS. Although four patients now have completely normal blood and marrow morphology, and another had normal blood and marrow morphology at the time of death due to unrelated disease, the study confirms the high incidence of cytopenia and morphological abnormality, sufficient to justify a diagnosis of MDS, in patients with a history of AA. No definite survival plateau was identified. However, the natural history of MDS secondary to AA seems to be different to that of MDS arising de novo; the clinical course is relatively indolent, possibly implying a different biology.

Adolescent↗
PubMed1994

Vasculitis in patients with systemic sclerosis and severe digital ischaemia requiring amputation.

OBJECTIVES: To document the incidence of histological vasculitis in amputation specimens from patients with severe digital ischaemia secondary to systemic sclerosis (SSc), and to look for an association between anticardiolipin (aCL) antibodies and severe digital ischaemia in SSc. METHODS: This was a retrospective review of patients with SSc who underwent amputation for digital ischaemia over a three year period. RESULTS: Five of nine patients had histological vasculitis, four of whom had aCL antibodies, although these were not present in high titre. CONCLUSION: Vasculitis does occur in SSc, at least in that subgroup with severe peripheral ischaemia. These findings could have implications for treatment of this subgroup of patients with SSc.

Adult↗
PubMed1994

Histological, radiological, and biochemical features of the adynamic bone lesion in continuous ambulatory peritoneal dialysis patients.

Adynamic bone is being found with increasing frequency in dialysis patients. Little is known about its aetiology, and even less about its natural history. We found 10 cases of asymptomatic adynamic bone among a group of 32 continuous ambulatory peritoneal dialysis patients, most of whom had never been exposed to aluminium-containing phosphate binders. Compared to the remaining 22 patients, they had an older mean age (54 +/- 11.4 vs. 42 +/- 11.8 years; p < 0.05), probably a longer pre-dialysis duration of renal failure (10.9 vs. 7.1 years), higher mean ionized calcium (1.30 +/- 0.04 vs. 1.15 +/- 0.02 mmol/l; p < 0.01), and lower mean intact parathyroid hormone (31.5 vs. 200.3 pg/ml; p < 0.001). The bone density was not different between the two groups, but 9 of the 10 adynamic patients had significant vascular calcification seen on plain radiology as compared with only 7 of 20 in the comparison group (p < 0.05). Follow-up of the adynamic patients showed a close association with serum intact parathyroid hormone and ionized calcium levels. With one exception, adynamic bone did not appear to be associated with lower bone density than other types of osteodystrophy, but a longer-term study is required to determine the complete natural history of this lesion.

Adult↗
PubMed1994

Inflammatory cells in normal human fracture healing.

We studied inflammatory cells in specimens of callus taken from normally healing human fractures. Using immunohistochemistry, T-cells, B-cells, macrophages, HLA-DR expression and endothelial proliferation were assessed. Macrophages were present from an early stage but became less numerous later. T-cells were initially specifically recruited into the fracture site at the stage of granulation tissue, but subsequently excluded from areas of bone and cartilage formation. Inflammatory cells may control and coordinate fracture healing as has been proposed for soft tissue wound healing. The most likely mechanism for this is by the cytokines and growth factors which they are known to release.

Adult↗
PubMed1993

Dermal dendrocytes in Dupuytren's disease: a link between the skin and pathogenesis?

The skin has previously been implicated in the process of Dupuytren's disease. The dermal dendrocyte is a factor XIIIa positive cell, which has been found in normal skin and some pathological conditions associated with fibrosis. In this study we examined the distribution of factor XIIIa positive cells in and around tissue from Dupuytren's disease. Immunohistochemistry was performed using a panel of antibodies for factor XIIIa, macrophages (CD68 and MAC387) and MHC II. Many factor XIIIa positive dendritic cells were present in and around Dupuytren's tissue; fewer CD68 and MHC II positive cells and very few MAC387 cells were seen. We propose that the factor XIIIa positive cells are dermal dendrocytes. This study may indicate an important link between the skin and pathogenesis of Dupuytren's disease.

Dendritic Cells↗
PubMed1993

Changes in numbers of epidermal cell adhesion molecules caused by oral cyclosporin in psoriasis.

AIM: To determine the effects of a three month course of low dose cyclosporin on the expression of epidermal cell adhesion molecules. METHODS: Eighteen patients with psoriasis were treated for 12 weeks with either 2.5 or 5 mg/kg/day of oral cyclosporin. Biopsy specimens taken from skin before, during, and after cyclosporin treatment were stained immunohistochemically for CD 54 (ICAM-1), CD 29 (beta-1 integrins), and CD18 (beta-2 integrins). RESULTS: There was a highly significant (p < 0.01) clinical response after 12 weeks of cyclosporin as assessed by the Psoriasis Area and Severity Index (PASI) score. The staining of CD 29 on keratinocytes of affected and unaffected psoriatic skin was not affected by cyclosporin. Epidermal CD54 was variably expressed in active psoriatic plaques and changed unpredictably after cyclosporin (p = NS). Staining for CD18 on large epidermal dendritic cells was reduced after cyclosporin (p < 0.02). The expression of CD18 by large epidermal dendritic cells during treatment correlated strongly with the PASI score at that time and one month after stopping cyclosporin (p < 0.02). CONCLUSIONS: Persistence of epidermal staining for CD 54 in psoriasis is compatible with a good clinical response to cyclosporin. Residual staining for CD 18 on large epidermal dendritic cells may be a useful marker for early clinical relapse.

Antigens, CD↗
PubMed1992

Regulation of 1 alpha, 25-dihydroxyvitamin D3 synthesis in macrophages from arthritic joints by phorbol ester, dibutyryl-cAMP and calcium ionophore (A23187).

Phorbol 12-myristate 13-acetate (100 nM), a potent protein kinase C and macrophage activator, has a biphasic affect on 25(OH)D3-1 alpha-hydroxylase activity in synovial fluid macrophages from arthritis patients. After 5 h, 1 alpha, 25(OH)D3 synthesis fell from 5.2 +/- 0.1 to 1.6 +/- 0.2 pmol/h per 10(6) cells, however, after 24 h and 48 h, synthesis increased to 17.4 +/- 0.3 and 22.3 +/- 1.4 pmol/h per 10(6) cells, respectively. Although an independent short-term mechanism is suggested, protein kinase C may promote macrophage activation, thus increasing long-term 25(OH)D3-1 alpha-hydroxylase expression. Intracellular calcium and cAMP are unlikely to activate the enzyme, since 0.1 microM of the calcium ionophore, A23187, and 1 mM dibutyryl-cAMP inhibited synthesis by 87% and 79%, respectively, after 24 h.

Arthritis↗
PubMed1992

Direct observation of the magnetization exchange dynamics responsible for magnetization transfer contrast in human cartilage in vitro.

Saturating irradiation far off-resonance can lead to diminution in the water signal seen in MRI, giving rise to magnetization transfer contrast. This results from transfer of magnetization between "solid" protons with restricted motion, which give rise to a band some tens of kilohertz wide, and the narrow signal from mobile protons. In the work reported here a high-power pulse spectrometer, which can detect signals from both mobile and immobile protons, was used to investigate the dynamics of magnetization transfer in cartilage in vitro. Magnetization transfer in modified Hoffman-Forsén inversion transfer experiments was well-described by a single rate constant model; full analytical solutions are offered for the resultant biexponential magnetization recovery curves. The use of pulsed methods to generate magnetization contrast may in some circumstances offer advantages over the steady-state saturation methods used hitherto.

Adult↗