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D C Mangham

Publications and source records attributed to D C Mangham.

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

Role of glutathione in cisplatin resistance in osteosarcoma cell lines.

This study was designed to examine whether and how glutathione and catalase increase the resistance of osteosarcoma cells to the toxicity of cisplatin. Eight osteosarcoma cell lines were exposed to varying concentrations of cisplatin, and a [3H]thymidine incorporation study then estimated their drug sensitivity. Cells were pretreated with aminotriazole and buthionine sulfoximine to depress catalase and glutathione activities and then entered into the same protocol to assess their sensitivity to cisplatin. Intracytoplasmic levels of catalase and glutathione were measured before and after the treatments. Cisplatin-glutathione conjugates were created to examine how glutathione might depress the toxicity of cisplatin. Although the cell lines differed in the magnitude of their response to cisplatin, there was a statistical correlation between intrinsic glutathione content and cisplatin resistance. Pretreatment with aminotriazole reduced catalase activity by 84% but did not change the sensitivity to cisplatin. Depletion of glutathione activity by 70% increased the sensitivity of the cells to the cytotoxicity of cisplatin. In addition, cisplatin was detoxified following conjugation with glutathione. The increased sensitization to cisplatin toxicity caused by the depletion of glutathione and cisplatin detoxification after the in vitro reaction of glutathione to cisplatin indicated that the formation of the glutathione-cisplatin conjugate was an important mechanism in the cellular resistance to cisplatin. These data also demonstrated that catalase activity did not contribute to resistance to cisplatin and suggested that H2O2-induced oxidative stress did not significantly contribute to the cytotoxicity of cisplatin in osteosarcoma cells.

Adenosine Triphosphate↗
PubMed1998

The 'penumbra sign' on T1-weighted MR imaging in subacute osteomyelitis: frequency, cause and significance.

OBJECTIVE: We studied the frequency and cause of a feature exhibited on T1-weighted (T1-W) magnetic resonance (MR) imaging termed the 'penumbra sign' in a series of patients presenting with osteomyelitis and correlated it with the double-line sign described as a T2-weighted (T2-W) or short tau inversion recovery (STIR) feature of both the Brodie's abscess and avascular necrosis. MATERIALS AND METHODS: The clinical, radiographic, MR imaging, microbiological and histological findings in 32 patients referred to an orthopaedic oncology service, but subsequently proven to have osteomyelitis, were reviewed. The presence or absence of a rim of tissue lining an abscess cavity typified by minor signal hyperintensity relative to the main abscess contents on T1-W MR imaging (the 'penumbra sign') was identified. The sign was correlated with the radiographic and other findings. RESULTS: The penumbra sign was identified in 24 cases (75%) and appears to be a more sensitive sign than the corresponding double-line sign which was evident in only 29% of these on T2-W or fast STIR images. The lesions were unilocular in 11 cases (46%) and multilocular in 13 (54%). The thickness of the penumbra ranged from 2 to 5mm. On histological examination the tissue comprising the penumbra sign was found to be highly vascularized granulation tissue containing thick walled arterioles. CONCLUSION: The penumbra sign is characteristically seen on T1-W MR images in subacute osteomyelitis and is due to a thick layer of highly vascularized granulation tissue which may not be visible as the double-line sign on T2-W or fast STIR sequences. This characteristic, but not pathognomonic, MR finding supports the diagnosis of bone infection and helps to exclude the presence of a tumour.

Abscess↗
PubMed1998

The normal structure and function of CD44 and its role in neoplasia.

CD44 is a transmembrane glycoprotein, the variant isoforms of which are coded for by alternative splicing, with the most prolific isoform being CD44 standard. CD44 is found in a wide variety of tissues including the central nervous system, lung, epidermis, liver, and pancreas, whereas variant isoforms of CD44 (CD44v) appear to have a much more restricted distribution. Variants of CD44 are expressed in tissues during development, including embryonic epithelia. Known functions of CD44 are cellular adhesion (aggregation and migration), hyaluronate degradation, lymphocyte activation, lymph node homing, myelopoiesis and lymphopoiesis, angiogenesis, and release of cytokines. The functions of CD44 are principally dependant on cellular adhesion in one setting or another. The role of CD44 in neoplasia is less well defined, although metastatic potential can be conferred on non-metastasising cell lines by transfection with a variant of CD44 and high levels of CD44 are associated with several types of malignant tumours. The physiological functions of CD44 indicate that the molecule could be involved in the metastatic spread of tumours. Many studies have investigated the pattern of CD44 distribution in tumours and some observations suggest that certain cells do not use CD44 in tumorigenesis or in the production of metastases. However, the data are extremely conflicting, and further studies are needed to establish the prognostic value of CD44 and its variant isoforms. The precise function of CD44 in the metastatic process and the degree of involvement in human malignancies has yet to be established fully.

Antigens, Neoplasm↗
PubMed1998

Soft-tissue amyloidoma. A case report.

A myloidoma of soft tissue is rare and there have been no previously published reports of limb involvement. We describe a case in which the tumour was present in the popliteal fossa. There was no evidence of systemic amyloid disease or of malignant neoplasm one year after the diagnosis.

Adult↗
PubMed1997

Epstein-Barr virus in B-cell lymphomas associated with chronic suppurative inflammation.

Chronic antigenic stimulation is considered to play an important role in neoplastic lymphoid transformation. This paper describes three cases of non-Hodgkin lymphomas (NHLs) associated with long-standing chronic suppuration. Two were primary bone lymphomas associated with long-standing chronic osteomyelitis and one was a primary skin lymphoma associated with chronic venous ulcers with a latent period of 13 years. All were diffuse large B-cell lymphomas, with plasmacytoid differentiation in two cases. Epstein-Barr virus (EBV)-encoded RNAs were demonstrated in virtually all tumour cells in all cases by in situ hybridization. Immunohistochemistry revealed EBV-encoded latent membrane protein (LMP)-1 expression in one case and BZLF1 protein expression in all three cases, whilst the EBV-encoded nuclear antigen (EBNA)-2 was not detected. Kaposi's sarcoma-associated herpesvirus (KSHV) sequences were absent in two cases studied. Our cases show similarities with pyothorax-associated pleural lymphomas reported mainly from Japan and recently from France, which are invariably associated with EBV. These findings suggest a causal effect of EBV in the development of this type of lymphoma complicating long-standing chronic suppuration. Localized immunodepression induced by chronic inflammation or immunosuppressive cytokines may favour the clonal proliferation of EBV-infected B cells.

Aged↗
PubMed1997

Fluid-fluid level in an intraosseous ganglion.

A case of an intraosseous ganglion with a fluid-fluid level visualised on MR imaging is presented. We discuss its possible pathogenesis and review other lesions that may exhibit this sign.

Adult↗
PubMed1997

Ewing's sarcoma presenting as a solitary bone cyst.

This report describes a rare case of Ewing's sarcoma presenting as a cystic lesion in the proximal humeral metaphysis. The clinical, pathological and radiological findings are described and discussed, with emphasis on the radiological appearances.

Biopsy↗
PubMed1997

Scintigraphically negative skip metastasis in osteosarcoma.

The accurate pre-operative evaluation of the intramedullary extent of osteosarcoma is essential, as it determines the level of bone resection. Radiographs, isotope bone and MR imaging scans have been considered as reliable in detecting skeletal metastasis and skip lesions. We report a case of osteosarcoma of the distal femur with a large skip lesion proximally which was not visualized by either routine radiography or bone scintigraphy, and was not included within the scan field on the initial MR imaging scan. The implications on patient management and possible reasons for failure of imaging to reveal the skip metastasis are discussed.

Adolescent↗
PubMed1997

Detection of interleukin-1 in the cartilage of patients with osteoarthritis: a possible autocrine/paracrine role in pathogenesis.

The interleukin-1 (IL-1) cytokines stimulate the synthesis of degradative enzymes in joint tissues and may play a role in the pathological joint destruction in osteoarthritis (OA). In this study, we have used immunohistochemistry and Western blot analysis to identify IL-1 in human OA cartilage. IL-1 alpha and IL-1 beta were evident in chondrocytes at the articular surface, as well as distributed throughout the cartilage. In many specimens, IL-1 beta but not IL-1 alpha was detected as a diffuse staining of the extracellular matrix especially surrounding superficial zone chondrocytes. Although chondrocyte-associated IL-1 alpha and IL-1 beta were detected in most specimens, cartilages exhibiting early osteoarthritic changes had the highest intensity of staining and the highest frequency of positive cells. Western blot analysis revealed intense immunoreactive bands corresponding to the 35 kDa precursor form of IL-1 alpha in all four chondrocyte lysates tested. The processed 18 kDa IL-1 beta species was present in only one of four chondrocyte lysates, and there was no clear evidence of precursor form within these cells. The results of this study indicate increased IL-1 alpha in cartilage showing early degenerative changes, suggesting an autocrine/paracrine role for this cytokine in OA pathogenesis.

Adult↗
PubMed1996

P-glycoprotein is expressed in the mineralizing regions of the skeleton.

Using oligonucleotide primers specific for the human MDR 1 gene, we were able to identify a specific amplicon using RT-PCR from total bovine growth plate chondrocyte RNA. The identification of MDR mRNA in growth plate chondrocytes led us to examine the precise distribution of MDR P-glycoprotein in bone and cartilage. We applied two monoclonal antibodies (C219 and C494) to human fetal, neonatal, and childhood growth plates and bone. In growth plates, P-glycoprotein was detected at high levels in a perilacunar distribution in the calcifying zone and at lower levels in hypertrophic, but not proliferative or reserve zone, chondrocytes. P-glycoprotein was also observed in perichondrial chondrocytes, in perivascular chondrocytes and matrix in the fetal cartilage anlage, and in osteoblasts and the surface osteoid matrix of newly formed bone trabeculae in the primary spongiosa. The recently described chloride channel of P-glycoprotein suggests a potential role of P-glycoprotein in growth plate chondrocyte hypertrophy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Giant cell tumor of the pancreas arising in the ovarian-like stroma of a mucinous cystadenocarcinoma.

We describe a malignant mucinous cystic neoplasm of the pancreas with ovarian-like stroma within which an osteoclast-like giant cell rich tumor arose. This rare tumor had a unique immunohistochemical profile with the giant cells staining for vimentin, leukocyte common antigen, and the monocyte/macrophage marker CD68, whereas the mucinous epithelium stained for epithelial membrane antigen and cytokeratin. The immunohistochemical findings are consistent with two lines of differentiation, one epithelial and the other suggesting mesenchymal differentiation of the giant cell tumor with an immunophenotype similar to giant cell tumor of bone. The coexistence of these two rare tumors suggests that they are histogenetically related. The findings of a giant cell tumor arising in the ovarian stroma indicates that the stroma of mucinous tumors is not always an innocuous component of the tumor.

Aged↗
PubMed1995

p53 overexpression in Ewing's sarcoma/primitive neuroectodermal tumour is an uncommon event.

Aim-To determine the presence of p53 overexpression in Ewing's sarcoma/primitive neuroectodermal tumours (ETs) and to assess whether p53 accumulation has any prognostic value.Methods-From a prospectively compiled database of 76 patients with ETs, suitable tumour tissue was available for 38. The monoclonal antibody pAb1801 was used to detect p53 nuclear protein overexpression. Results-Nuclear staining was detected in the tumours of three (8%) of the 38 patients. Where tumours stained positively, over 10% of the tumour nuclei were postively stained. All three patients whose tumours overexpressed p53 died and in a relatively short time compared with the patients who did not overexpress p53 (mean 3.7 months compared with a mean of 38.7 months in the p53 negative group).Conclusion-Overexpression of p53 in ETs is an uncommon event. Overexpression of p53 has repeatedly been shown to correlate closely with p53 point missense mutations and therefore this oncogenic event appears not to be of primary pathogenic importance in ETs. There is a tentative indication that those uncommon ETs in which p53 overexpression can be detected may be-have more aggressively.

Journal Article↗
PubMed1994

Expression of proliferating cell nuclear antigen (PCNA) in gastric carcinoma: no evidence for prognostic value.

It has been proposed that immunostaining with PC10, a monoclonal antibody against proliferating cell nuclear antigen (PCNA), is of prognostic value in gastric carcinoma. Gastric carcinomas from a series of 90 patients in whom survival data were known have been studied. There was no relation between the degree of PC10 immunostaining assessed semiquantitatively and survival.

Adenocarcinoma↗
PubMed1994

Oxygen scavengers in simple bone cysts.

Simple bone cyst is a fluid-filled, cystic lesion that occurs in the metaphysis of the long bones of children and adolescents. The chemical characteristics of the cyst fluid of the simple bone cyst are similar to those of serum. The existence of the cyst fluid itself may be an obstacle to cyst healing, and, in part, this may be because the cyst fluid contains bone destructive factors. Oxygen-free radicals, which are cytotoxic and cause connective tissue damage, are known to be generated under ischemic conditions. Blockage to the drainage of interstitial fluid within the metaphysis has been suggested as the possible primary cause of simple bone cyst, thus causing an ischemic state in which free radicals are generated. The precise measurement of free radical levels is difficult to obtain because of their extremely short half-lives. High levels of oxygen-free radicals induce high levels of oxygen scavengers locally to protect cells from the harmful effects of the free radicals. Therefore, the activity of the oxygen scavengers, superoxide dismutase and catalase, was measured in the cyst fluid of 9 cases of simple bone cyst as an indicator of high oxygen-free radical content in the cyst. Serum from the patients with simple bone cyst and joint fluid from patients with osteoarthritis were used for comparison with the intracystic levels of oxygen scavengers. Superoxide dismutase activity was directly measured at room temperature using an electron spin resonance spin-trapping technique with 5,5'-dimethyl-1-pyrroline-N-oxide as a trapping agent.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Epstein-Barr virus and carcinomas: rare association of the virus with gastric adenocarcinomas.

We have analysed 174 gastric carcinomas from the United Kingdom and from Japan for the presence of Epstein-Barr virus (EBV) using in situ hybridisation for the small EBV-encoded nuclear RNAs (EBERs). EBV was detected in the tumour cells in all of six undifferentiated gastric carcinomas with prominent lymphoid stroma (undifferentiated carcinomas of nasopharyngeal type, UCNT) but only in three of the remaining 168 typical gastric adenocarcinomas (1.8%). No differences were observed between the British and the Japanese cases. One case with an EBV-positive UCNT showed adjacent areas of EBV-negative typical adenocarcinoma. It is uncertain whether these patterns represent two independent carcinomas or whether they are the result of heterogeneous EBV infection in a single tumour. In the remaining EBV-positive carcinomas, viral transcripts were detected in virtually all tumour cells, indicating that EBV infection must have taken place early in the neoplastic process and suggesting that the virus is likely to be of pathogenetic significance for the virus-associated tumours. Immunohistology demonstrated absence of detectable levels of the EBV-encoded latent membrane protein, LMP1, and nuclear antigen, EBNA2. The BZLF1 protein which induces the switch from latent to lytic infection was demonstrated in a small proportion of the tumour cells in three cases. The close association of EBV with undifferentiated gastric carcinomas compared to the variable association with gastric adenocarcinomas suggests fundamentally different roles for the virus in the aetiology of these two malignancies.

Adenocarcinoma↗
PubMed1993

Complement and the recruitment of mononuclear osteoclasts.

AIM: To investigate the hypothesis that complement mediates the recruitment of mononuclear osteoclast precursors to the exposed mineralised bone surface. METHODS: Synthetic hydroxyapatite was incubated in vitro with fresh human serum, with and without complement activation inhibitors. Assays for complement components and the generation of the C3 breakdown product C3d were done. C3 deposition in human fetal tibia primary spongiosa was localised immunohistochemically and complement receptors CR1, CR2, CR3, and CR4 were localised cellularly. Immunohistochemical and enzyme histochemical characterisation of the mononuclear and multinuclear osteoclasts was made with emphasis on their association with complement C3 deposition. RESULTS: Components of complement bind to synthetic hydroxyapatite crystals and, at lower concentrations, C3d was generated in the fluid phase. C3 was deposited in a focal and linear distribution on newly formed bone trabecular surfaces in the primary spongiosa. In a similar distribution CD61, CD68, and tartrate resistant acid phosphatase positive mononuclear osteoclasts were shown in close apposition to the bone trabecular surface. These mononuclear osteoclasts, unlike multinucleate osteoclasts, expressed the complement receptors CR3 and CR4. CR1 and CR2, however, could not be shown on either mononuclear or multinuclear osteoclasts. CONCLUSION: It is suggested that C3 deposition on mineralised bone surfaces mediates the recruitment of mononuclear osteoclasts to this site. As the mononuclear osteoclasts fuse to form the multinucleate osteoclast, complement receptor expression is lost.

Bone Development↗