Biomedical subjects
Publications and source records attributed to J Crocker.
A patient with unilateral tonsillar enlargement secondary to locally invasive candidal infection is presented. This was not associated with any history of immunosuppression or prolonged use of broad-spectrum antibiotics. Invasive candidal infection of the tonsil has not previously been reported.
The murine monoclonal antibody BU31 binds to the nuclear membrane of many cell types. The expression of the BU31 antigen has previously been shown to have an inverse correlation with the proliferative index in lung tumours, defined by Ki67 staining. The distribution of BU31-positive cells is now shown to parallel the distribution of non-dividing cells in a range of normal human and rat tissues, although neuroendocrine cells and germ cells in the testis show no reactivity. Cells grown in culture and induced to undergo growth arrest show a higher level of labelling with BU31 than their proliferating counterparts. Confocal laser scanning microscopy reveals that the BU31 antigen is distributed predominantly along the nuclear lamina, with occasional internal foci. This distribution is very similar to that of the nuclear membrane proteins lamin A and lamin C, suggesting that the BU31 antigen and lamins A and C could be one and the same. Immunoblotting using recombinant lamin proteins confirmed this proposal. Moreover, a monoclonal antibody to the non-proliferation-associated antigen, statin, also recognizes lamins A and C. These data indicate that the demonstration of lamins A and C can be used to provide information on the proliferative activity of normal and neoplastic tissues. These data also suggest a role for nuclear lamins A and C during cellular quiescence, possibly through the reorganization and maintenance of nuclear structure, or more directly through interactions with the retinoblastoma gene product or related proteins.
Explore the source record for details and available documents.
Infiltration by T lymphocytes into oesophageal carcinomas was assessed immunohistochemically, total T lymphocyte numbers by staining for CD3 and activated T lymphocytes by staining for CD25. Five squamous carcinomas and seven adenocarcinomas, resected without neoadjuvant treatment, were studied. Computer aided quantitation showed that total numbers of tumour infiltrating CD3 positive cells were highly variable (range 48-1673 cells/mm2). They were located largely in the stromal (87.9-99.2%) rather than intratumoral regions. Up to 84% of tumour infiltrating T lymphocytes were CD25 positive, although the median figure was 33%. There was no correlation between T lymphocyte infiltration or activation and expression of class I and II histocompatibility antigens, intercellular adhesion molecule-1, tumour stage or grade. These results imply that the local inflammatory response in oesophageal carcinomas is deregulated, which may be a factor contributing to the aggressive nature of the tumours.
Explore the source record for details and available documents.
BACKGROUND: The multidrug resistance marker P-glycoprotein (P-gp) was studied immunohistochemically in 78 primary malignant lung tumours. P-gp is a 170 kD transmembrane ATP dependent drug efflux pump which has been shown to be important in the resistance of some tumours to chemotherapy. Certain normal tissues express P-gp and tumours derived from these tissues are often insensitive to cytotoxic agents, showing raised P-gp levels innately or following chemotherapy or radiotherapy. METHODS: Samples from 78 patients undergoing surgery for primary malignant lung tumours were snap frozen and stained immunohistochemically using the monoclonal antibody C219 which reacts with a P-gp epitope. None of the study group had received chemotherapy or radiotherapy before surgery was performed. RESULTS: Twenty seven of the 78 lung tumours (34.6%) showed immunohistochemically detectable levels of P-gp which varied with tumour type; 17 of 54 squamous cell carcinomas (31.5%), seven of 15 adenocarcinomas (46.7%), and neither of two small cell carcinomas showing positive staining. In six of seven cases normal respiratory epithelium present showed the presence of P-gp. CONCLUSIONS: P-gp is immunohistochemically detectable in frozen tissue from a proportion of malignant lung tumours before exposure to radiotherapy or drugs associated with multidrug resistance. It may have a role in tumour resistance to cytotoxic drugs, but further clinical studies will be required to evaluate any correlation between P-gp levels and response to treatment.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
p53 is a nuclear phosphoprotein which acts as a tumour suppressor factor, regulating cell growth and division. Mutations in the p53 gene appear to be the most common genetic alterations in human cancer. The aim of this study was to investigate p53 expression in laryngeal squamous cell carcinomas and to assess its role as a marker of prognostic significance. Using immunohistochemical staining techniques, a series of laryngeal carcinomas (n = 87) were examined for expression of the mutant form of p53 phosphoprotein using the monoclonal antibody PAB 1801. p53 over-expression was noted in 50 biopsies of laryngeal carcinomas (57.5%) but not in any of the non-neoplastic laryngeal mucosa which were used as the control. There was no statistical correlation between p53 immunoreactivity and the clinicopathological parameters of the cancers including: site of tumour, TNM staging, differentiation grading and tumour recurrence. These findings indicate that p53 expression is strongly associated with carcinoma cells and not with normal cells in the larynx. However, p53 expression is probably unrelated to the biological aggressiveness of these tumours.
AIM: To examine the expression of HLA-ABC and HLA-DR major histocompatibility (MHC) antigens and intercellular adhesion molecule (ICAM)-1 in normal, inflamed, metaplastic, and neoplastic oesophageal tissue and in freshly disaggregated tumours. METHODS: Sequential sections of frozen tissue and cytospins of freshly disaggregated tumour were stained using the ABC peroxidase system and monoclonal antibodies specific for HLA-ABC, HLA-DR and ICAM-1. RESULTS: Normal oesophageal tissue showed positive staining for HLA-ABC in the basal layers of the oesophageal squamous epithelium and on the epithelial cells of the submucosal oesophageal glands. HLA-DR and ICAM-1 were not detected in either of these cell types. In 20 of 37 (54%) carcinomas HLA-ABC was expressed weakly, with heterogeneous expression in nine (24%). Two tumours showed strong expression of HLA-ABC, but 15 of 37 (41%) were negative. HLA-DR and ICAM-1 were expressed weakly in six of 37 (16%) carcinomas without correlation with each other or with the expression of HLA-ABC. CONCLUSIONS: HLA-ABC is absent from a high proportion of oesophageal carcinomas (41%) and is otherwise variably and weakly expressed with strong expression in only a small fraction (3%). In other carcinomas there is a higher level of HLA-ABC expression. This discrepancy may partly explain the aggressive nature of oesophageal carcinomas. HLA-DR and ICAM-1 are not normally expressed on those cells from which oesophageal carcinomas are thought to arise. The limited expression found here could suggest a partial or inhibited immune response against oesophageal carcinoma. In vivo repressive factors may be involved.
Aim-To determine the effects of hepatocyte growth factor (HGF) on myeloid cell differentiation and cMET expression using the promyelocytic HL60 cell line.Methods-HL60 cells cultured with purified recombinant HGF, dimethyl sulphoxide (DMSO), or 12-O tetradecanoylphorbol-13-acetate (TPA) were immunostained for the differentiation markers, human neutrophil elastase (HNE), cathepsin B, MAC387, or the receptor for hepatocyte growth factor (cMET).Results-HGF treated cells were positive on staining for cathepsin B and MAC387, but were negative for HNE, indicating monocytic differentiation. HGF treated cells had the morphology of monocytes but continued to divide at the same rate as control cells and remained non-adherent. DMSO treated cells were positive for HNE and cell numbers were reduced, confirming myeloid differentiation. TPA treated cells were positive for cathepsin B and MAC387, cell numbers were reduced, and the cells became adherent, confirming terminal monocytic differentiation. Untreated HL60 cells were weakly positive for cMET at the start of the culture period and expression increased after 72 hours. Cells treated with HGF, DMSO, or TPA were also positive for cMET.Conclusions-These data suggest that HGF induced partial monocytic differentiation in HL60 cells. In addition, expression of cMET by HL60 cells occurs at an early stage in myelomonocytic cells and is maintained after differentiation along either the myeloid or monocytic pathways.
Aims-To determine whether neutrophil elastase and cathepsin G are expressed, at transcriptional or translational levels, in the bone marrow from a patient with Chediak-Higashi syndrome.Methods-Blood neutrophils were isolated from three patients with Chediak-Higashi disease and bone marrow was collected from one. Cell lysates were analysed for neutrophil elastase and cathepsin G activity by enzyme linked immunosorbent assay and western immunoblotting. Northern blotting was used to detect messenger RNA (mRNA) for cathepsin G, elastase and beta-actin in bone marrow extracts, and immunohistochemistry was used to localise the enzymes in marrow myeloid cells.Results-Elastase and cathepsin G were not detected in blood neutrophils from the patients with Chediak-Higashi disease, but were present in bone marrow cells, although immunohistochemistry showed they were not within cytoplasmic granules. The concentrations of elastase and cathepsin G in Chediak-Higashi bone marrow were about 25 and 15%, respectively, of those in normal marrow. Quantitative scanning of northern blots showed that elastase and cathepsin G mRNA, corrected for beta-actin mRNA, were expressed equally in normal marrow.Conclusions-Transcription of elastase and cathepsin G mRNA in promyelocytes of patients with Chediak-Higashi disease is normal, but the protein products are deficient in these cells and absent in mature neutrophils. This suggests that the translated proteins are not packaged into azurophil granules but are degaded or secreted from the cells.
Aim-To examine the expression of CD40 and B7 (CD80) antigens and the CD40 ligand in Hodgkin's disease.Methods-Antigen and ligand expression was studied in 17 cases of Hodgkin's disease using immunohistochemistry. The study included 11 cases of Hodgkin's disease in which latent Epstein-Barr virus (EBV) infection could be demonstrated within tumour cells by in situ hybridisation for the EBV encoded early RNAs (EBERs).Results-In all cases, irrespective of EBV status, Reed-Sternberg cells and their variants (HRS cells) showed strong expression of both B7 and CD40 antigens. CD40 ligand expression was not shown in HRS cells but was confined to a subset of small lymphocytes some of which were seen to be in intimate contact with HRS cells.Paraffin wax sections from a further 60 cases of Hodgkin's disease were examined for CD40 and EBER expression alone. The CD40 antigen was identified in HRS cells in all of these cases irrespective of EBER expression.Conclusions-As CD40 and B7 expression are features of professional antigen presenting cells, these results provide further evidence that HRS cells may have antigen presenting properties and that this may contribute to the characteristic recruitment and activation of non-malignant lymphocytes which is a feature of Hodgkin's disease. The ability of HRS cells to activate T(h) cells may in turn contribute to their own survival through the induction of the gp39/CD40 pathway.
Paraffin wax sections of lymph node biopsies from a total of thirteen patients with the morphologic and clinical features of Castleman's disease were analyzed for the presence of the Epstein-Barr virus (EBV) by in situ hybridization for the noncoding EBV early RNAs (EBERs) and by immunohistochemistry for the EBV-encoded latent membrane protein-1 (LMP-1). Of twelve cases of localized Castleman's disease EBER-positive cells were identified in five, and in these cases were only rarely found and were always confined to the interfollicular regions. LMP-1 was not detected in any of these cases, either alone or after dual staining for EBERs and LMP-1. (A similar pattern of EBER expression is seen in nonneoplastic lymphoid tissue from EBV-positive individuals.) No EBER-positive or LMP-1 positive cells were identified in a single case of multicentric Castleman's disease. In two additional patients initially diagnosed with Castleman's disease of localized plasma cell type, repeat biopsy showed Hodgkin's disease. In both cases Reed-Sternberg cells and their variants were identified in the original biopsy on which the diagnosis of Castleman's disease was made. In one of these cases these cells showed expression of EBERs and LMP-1, indicating latent infection with EBV. The results suggest that EBV is not generally associated with Castleman's disease. Further analysis of a series of cases of multicentric Castleman's disease is indicated.
Explore the source record for details and available documents.
The production of the murine monoclonal antibody BU31 is described. This antibody identifies a nuclear envelope protein which is expressed in some but not all cells, and which resembles statin, a protein reported to be expressed by non-proliferating cells. BU31 was applied onto frozen sections of a series of 78 lung tumours and the staining patterns were compared with those obtained with Ki-67. There was an inverse correlation between the proportion of tumour nuclei labelled with the two reagents (r = -0.61, 95 per cent confidence intervals -0.73 to -0.45). However, the four neuroendocrine neoplasms were BU31-negative. Squamous cell carcinomas often showed a peripheral distribution of the cells stained positively with Ki-67, whereas BU31 tended to label centrally situated cells. These observations are consistent with the concept that the antigen recognized by BU31 is expressed by non-proliferating cells in these tumours.
Explore the source record for details and available documents.
The relationship between proliferating cell nuclear antigen (PCNA) expression and various clinicopathological indices (age, sex, tumour location, histological type and grade and treatment) and post-operative survival were studied in patients with central nervous system gliomas using univariate and multivariate analysis. The expression of PCNA (PC10 score) was examined immunohistochemically using the monoclonal antibody PC10 on paraffin sections from 45 cases. Univariate analysis showed that a high PC10 score as well as older age, high histological grade and the histological type (astrocytoma) were associated with reduced survival. However, multivariate analysis revealed that only PC10 score and histological type had independent prognostic significance. The most important feature influencing PC10 score was the tumour grade. Regarding the patients who relapsed, the survival from the time of original diagnosis was related to the relapse-free period, while the PC10 score of the primary tumour emerged as the only independent predictor of survival following the first recurrence. These results indicate that PCNA expression is an independent prognostic indicator in CNS gliomas.