The potential values of fractal dimension measurement in histopathology.
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Decision Making, Computer-Assisted↗
Biomedical subjects
J Crocker
Publications and source records attributed to J Crocker.
Silver-stained nucleolar organiser region counts are of no prognostic value in primary breast cancer.
The assessment of nucleolar organising regions have been reported to be of prognostic value both in a number of haematological and solid tumours. We have examined the relationship between the number of nucleolar organising regions (NORs) present in 75 primary breast cancers and various clinical and pathological features known to be associated with prognosis in patients with breast cancer. Formalin-fixed, paraffin-embedded tumour tissue was sectioned and stained by a one-stage argyrophil (AgNOR) method. Using light microscopy the mean number of AgNORs per cell was calculated. No correlation was observed between AgNOR counts and any of the prognostic variables studied, including oestrogen receptor (ER) status, histological grade of malignancy, lymph node stage or site of initial metastatic disease. Similarly there was no correlation between AgNOR counts and disease-free interval or survival. AgNOR counts do not appear to be a prognostic factor in primary breast cancer.
Adult↗
Epstein-Barr virus latent genes in tumour cells of Hodgkin's disease.
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Antigens, Nuclear↗
Epstein-Barr virus (EBV)-associated lymphoproliferative disease in the SCID mouse model: implications for the pathogenesis of EBV-positive lymphomas in man.
When human peripheral blood lymphocytes (PBLs) from Epstein-Barr virus (EBV)-seropositive donors are injected intraperitoneally into SCID mice, EBV+ B cell tumors develop within weeks. A preliminary report (Mosier, D. E., R. J. Gulizia, S. M. Baird, D. D. Richman, D. B. Wilson, R. I. Fox, and T. J. Kipps, 1989. Blood. 74(Suppl. 1):52a) has suggested that such tumors resemble the EBV-positive malignancy, Burkitt's lymphoma. The present work shows that generally the human (hu) PBL-SCID tumors are distinct from Burkitt's lymphoma and instead resemble lymphoblastoid cell lines (LCLs) generated by EBV-infection of normal B cells in vitro in terms of: (a) their cell surface phenotype, with expression of B cell activation antigens and adhesion molecules, (b) normal karyotype, and (c) viral phenotype, with expression of all the transformation-associated EBV latent proteins and, in a minority of cells, productive cycle antigens. Indeed, in vitro-transformed LCLs also grow when inoculated into SCID mice, the frequency of tumor outgrowth correlating with the in vitro growth phenotype of the LCL which is itself determined by the identity of the transforming virus (i.e., type 1 or type 2 EBV). Histologically the PBL-derived hu-SCID tumors resemble the EBV+ large cell lymphomas that develop in immuno-suppressed patients and, like the human tumors, often present at multiple sites as individual monoclonal or oligoclonal foci. The remarkable efficiency of tumor development in the hu-SCID model suggests that lymphomagenesis involves direct outgrowth of EBV-transformed B cells without requirement for secondary genetic changes, and that selection on the basis of cell growth rate alone is sufficient to explain the monoclonal/oligoclonal nature of tumor foci. EBV+ large cell lymphoma of the immunosuppressed may arise in a similar way.
Animals↗
Nucleolar ultrastructure in low- and high-grade non-Hodgkin's lymphomas.
Transmission electron microscopy was used to study the ultrastructure of nucleoli in seven high- and seven low-grade non-Hodgkin's lymphomas. Nucleoli with a single large fibrillar centre were predominantly seen in the low-grade group, while the majority of nucleoli in high-grade lesions contained several small fibrillar centres of approximately equal size. A third type of nucleolar appearance was identified, with a large central fibrillar centre surrounded by numerous small 'satellite' fibrillar centres. This nucleolar configuration was the least common but was more often seen in low-grade than in high-grade lymphomas. The mean fibrillar centre cross-sectional area was determined for each group and measured 278,800 nm2 for low-grade non-Hodgkin's lymphomas and 62,507 nm2 for high-grade lymphomas (P less than 0.001). These results show that fibrillar centre size and morphology correlates with grade of non-Hodgkin's lymphoma and may reflect differences in ribosomal deoxyribonucleic acid transcription.
Cell Nucleolus↗
CD23 expression in non-Hodgkin lymphoma: immunohistochemical demonstration using the antibody BU38 on paraffin sections.
The leucocyte antigen CD23 is upregulated in the early stages of B-cell activation by Interleukin-4 (IL-4), and functions as an IgE receptor and lymphocyte growth factor. We have studied the expression of CD23 in 68 cases of non-Hodgkin lymphoma (NHL) using the antibody BU38. This new antibody has the great advantage of being applicable to routinely-processed paraffin sections. CD23 was expressed in tumour cells in 27 out of 36 cases of low grade NHL and 3 out of 32 cases of high grade NHL. Follicular dendritic cells were strongly positive and were seen in follicular lymphomas. Macrophages were also positive and were numerous in high grade lesions.
Antigens, CD↗
The effect of inducing agents on the numbers of interphase fibrillar centers in the U937 promonocytic cell line.
The mean numbers of interphase fibrillar centers have been determined in triplicate experiments, using the argyrophil (AgNOR) method. Promonocytic U937 cells were incubated with each of three inducing agents, namely, interleukin-6, granulocyte-macrophage colony-stimulating factor, and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate. The cells were examined at 24, 48, and 72 h during the induction periods and their doubling time and mean AgNOR score were calculated. After 72 h, the cells were maintained in culture for a further 24 h in the absence of an inducing agent and these parameters were determined again. It was found that whereas the unstimulated U937 cells had a mean value in the region of 50 AgNORs per nucleus, this diminished to about 20 after a 72 h incubation, but rose to 30 or more when the inducing agents had been withdrawn for 24 h. These observation confirm the results of previous studies using melanoma and HL60 cell lines: however, it has now been demonstrated that a variety of agents can modulate the numbers of fibrillar centers in a very similar way in a single cell line. Furthermore, we have shown that the "undifferentiated" U937 cell AgNOR score recovers when the agents no longer act upon the cells; this implies that fibrillar center numbers are intimately related to differentiation state in cell lines, as in the case in, for example, tumor specimens.
Cell Count↗
Non-Hodgkin's lymphoma involving the tonsil: an immunohistochemical study.
Twenty-one patients with non-Hodgkin's lymphoma involving the palatine tonsil were studied in an attempt to relate pathological data to clinical outcome. Eleven tumours were classified as low-grade and ten as high-grade on morphological criteria. The results of immunohistochemical investigations are presented; all tumours but one were of B-cell origin. None of the pathological factors studied were found to be useful prognostic indicators.
Adult↗
Bone marrow hypervascularity in patients with myelofibrosis identified by infra-red thermography.
Infra-red thermography was used to assess bone marrow vascularity in six patients with myelofibrosis secondary to myeloproliferative disorders (four primary myelofibrosis and two primary proliferative polycythaemia). The technique was evaluated with conventional static and dynamic radio-isotopic imaging and with immunohistochemical staining of bone marrow biopsies. Infra-red thermography identified increased bone marrow blood flow in patients with established myelofibrosis and correlated with dynamic radio-isotopic studies of blood flow and hypervascularity identified by immunohistochemistry. Increased bone marrow blood flow and vascular proliferation was not confined to the central bone marrow but also extended into the peripheral marrow of the long bones. Endothelial cell proliferation may be an initiating event in the pathogenesis of myelofibrosis but evaluation of bone marrow vascularity and blood flow has hitherto relied on invasive and complicated techniques. This study has identified bone marrow hypervascularity in patients with myelofibrosis and shown infra-red thermography to be a simple non-invasive method of assessing vascularity. This non-invasive technique may be used to study disease progression and response to therapeutic regimens in patients with myelofibrosis and to study bone marrow blood flow in other bone marrow disorders.
Biopsy↗
Immunohistochemical demonstration of CD23 expression on lymphocytes in rheumatoid synovitis.
The leucocyte antigen CD23 is expressed by B lymphocytes following activation by a number of stimuli and functions as an IgE receptor, and in its soluble form, as a putative B cell growth factor. The expression of CD23 on the surface of lymphocytes in paraffin wax sections of synovial biopsy specimens was studied using a novel mouse monoclonal antibody, BU38. Specimens were investigated from nine cases of rheumatoid arthritis, six cases of osteoarthritis, and eight cases of chronic inflammation in articular and non-articular tissues. CD23 was expressed on a high proportion of lymphocytes in all forms of chronic inflammation and was not specific for rheumatoid arthritis. It may be a characteristic feature of any chronic inflammatory response. As CD23 was found on the surface of lymphocytes in many cases of these arthritides, sCD23 in serum or synovial fluid may yet prove a useful marker for the severity of the inflammatory infiltrate.
Adolescent↗
Interphase nucleolar organiser regions and survival in squamous cell carcinoma of the bronchus: a 10 year follow up study of 138 cases.
BACKGROUND: Good prognostic indicators for patients with squamous cell carcinoma of the lung would help to determine the most appropriate treatment for individual patients. METHODS: A silver colloid technique that shows interphase nucleolar organiser regions (AgNORs) has been applied to representative paraffin sections from 138 cases of squamous cell carcinoma of the bronchus treated by surgical resection of the primary tumour at East Birmingham Hospital in 1977. Of the 138 patients, 23 (17%) were alive 10 years after their operation. RESULTS: The mean (SD) AgNOR count per cell was significantly higher for all grades of malignancy (well differentiated 10.5 (2.6), moderately differentiated 10.7 (3.2), and poorly differentiated 12.7 (4.5)) than for normal pseudostratified columnar epithelium from non-affected areas (2.3 (0.78)). There was a trend for AgNOR counts to be higher in poorly differentiated tumours, but a wide range of AgNOR counts was observed in all histological grades. AgNOR counts did not predict clinical outcome, irrespective of the stage of the disease, and did not relate to DNA ploidy or the percentage of cells in the proliferation phase of the cell cycle. Nine of 47 patients (19%) with tumours classified as DNA diploid and eight of 63 patients (13%) with DNA aneuploid tumours were alive 10 years after operation. Principal component analysis identified the clinicopathological stage of disease as the variable best related to survival. The percentage of patients surviving 10 years was 30% for stage I, 20% for stage II, 10% for stage IIIa, 9% for stage IIIb, and none for stage IV. CONCLUSION: The AgNOR technique is not of prognostic value in postoperative patients with squamous cell carcinoma of the bronchus.
Adult↗
Epithelial cell type, clinical behaviour and AgNOR counts in thymic epithelial tumours.
The relationship between epithelial cell type, clinical behaviour and number of nucleolar organiser regions (AgNORs) was investigated in 37 thymomas and three thymic carcinomas. The thymomas were classified according to epithelial cell morphology as cortical (16 cases), medullary (8 cases) or mixed (13 cases). Seven cortical tumours had infiltrated the capsule or adjacent structures at the time of operation, whereas only one medullary and two mixed tumours showed evidence of invasion, the differences being statistically significant (P less than 0.01). None of the patients with medullary thymoma had myasthenia gravis, but there was a significantly higher incidence (P less than 0.001) among those with cortical or mixed tumours (six and three cases respectively). The mean AgNOR count for medullary tumours was 1.56, compared with 2.22 and 2.06 for cortical and mixed tumours. Although the counts for medullary tumours were significantly lower than for the other two types (P less than 0.01), there was considerable overlap. The mean count for the carcinomas was 4.94--significantly higher than for the thymomas (P less than 0.01)--but again overlap was considerable. No relationship was demonstrable between AgNOR counts, clinical stage, incidence of myasthenia or recurrence. It is concluded that although classification of thymomas based on epithelial cell type represents an improvement on previous classifications, it must be applied with caution. Similarly, AgNOR counts may give some indication of malignant potential, but their usefulness in individual cases is doubtful.
Adult↗
Comparison of antilymphocyte globulin and continuous i.v. cyclosporine A as induction immunosuppression for cadaver kidney transplants: a prospective randomized study.
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Antilymphocyte Serum↗
Changes in the expression of elastase and cathepsin B with differentiation of U937 promonocytes by GMCSF.
The human promonocytic cell line, U937, when treated for up to 72h with 12,O,tetradecanoyl-phorbol-13-acetate or granulocyte-macrophage colony-stimulating factor, exhibited increased phagocytic activity and expression of the marker p150/95. There was an associated increase in the monocyte proteinase cathepsin B and its mRNA but decreased cellular levels of neutrophil elastase and elastase mRNA. Granulocyte-macrophage colony-stimulating factor therefore causes differentiation of U937 cells, with appropriate effects on the synthesis of leukocyte proteinases.
Cathepsin B↗
Immunohistochemical determination of CD23 expression in Hodgkin's disease using paraffin sections.
The leukocyte antigen CD23 is expressed during B-cell development, and functions as an IgE receptor and a lymphocyte growth factor. We studied the expression of CD23 in paraffin sections of lymphoid tissue using the monoclonal antibody BU38. Fifteen cases of Hodgkin's disease, ten reactive lymph nodes, eight B-cell, and seven T-cell non-Hodgkin's lymphomas were analysed immunohistologically. CD23 positivity was seen on follicular dendritic cells and a small number of lymphocytes in reactive nodes. Thirteen of the 15 cases of Hodgkin's disease showed CD23 expression in both neoplastic cells and reactive lymphocytic infiltrate. The antigen was demonstrated in four of the B-cell and one of the T-cell tumours. CD23 may be important in mediating the mixed cellular infiltrate characteristic of Hodgkin's lymphoma.
Adolescent↗
Silver staining of nucleolar organizer region associated proteins using polyethylene glycol as the protective colloidal developer.
A simple modification to the silver staining technique for the demonstration of nucleolar organizer region associated proteins is described. Polyethylene glycol 20,000 is used instead of gelatin as the colloidal developer. This modified technique remains a one stage procedure that is quick and easy to perform. It results in reduced precipitate and less non-specific staining with specimens in which it had been previously difficult to demonstrate these intranuclear silver staining structures.
Animals↗
Relationship between intraepithelial neoplasia of the cervix and the size and number of nucleolar organizer regions.
A silver colloid technique was applied to 18 colposcopic biopsies of the cervix. These comprised 7 cases of cervical intraepithelial neoplasia I (CIN I), 5 cases of CIN II, and 6 cases of CIN III. The nucleolar organizer regions subsequently visualized (AgNORs) were enumerated using an oil immersion lens. The maximum diameters of the AgNORs and aggregates thereof were measured, by hand, from carefully calibrated monochrome photographs. The mean numbers of AgNORs subsequently identified steadily increased, whereas the mean sizes of AgNORs decreased from CIN I to CIN III. In CIN I the mean AgNOR number was 2.3 (range 1.8-3.4) and the AgNOR mean maximum diameter (Dmax) was 1.28 microns (range 0.75-1.75). In CIN II the mean number was 3.5 (range 3.1-4.6) and the AgNOR Dmax was 0.98 micron (range 0.9-1.18). In CIN III the mean number was 4.7 (range 4.0-6.1) and the Dmax was 0.62 micron (range 0.51-0.9). CIN III could be distinguished from CIN I and CIN II on the basis of AgNOR sizes, and an inverse relationship between AgNOR numbers and sizes was established.
DNA, Neoplasm↗