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Biomedical subjects

R C Curran

Publications and source records attributed to R C Curran.

At least 19 recordsLinked to original sources

Angiofollicular lymph node hyperplasia (Castleman's disease): an immunohistochemical and enzyme-histochemical study of the hyaline-vascular form of lesion.

Tissues from five cases of angiofollicular lymph node hyperplasia have been studied. All had the histological structure of the hyaline-vascular type of lesion; large numbers of very compact lymphoid follicles were distributed evenly throughout a highly vascular tissue. The follicles were characterized by their small size, a vascular poorly cellular and frequently hyalinized centre, and a 'tight' concentric mantle of small lymphocytes arranged in layers producing an 'onion-skin' appearance. The interfollicular tissue was characterized by the large numbers of small vessels mainly hyalinized capillaries and a few high endothelial venules and the presence of variable numbers of lymphocytes, plasma cells, immunocytes and immunoblasts. The immunoperoxidase method demonstrated polytypic cytoplasmic immunoglobulin in the small numbers of centroblasts and plasma cells within the follicle centres and in the plasma cells and immunocytes in the interfollicular tissue. Large numbers of suppressor T cells were present in the interfollicular areas and only scattered helper T cells were seen within the lymphocyte mantles. A strong reaction for factor VIII-related antigen was seen in the endothelium of the interfollicular high endothelial venules but only a weak reaction in the vessels in the follicle centres. A concentric distribution pattern of the dendritic reticulum cells was seen with the metalophil impregnation method of Marshall and with the enzyme histochemical methods for acid alpha-naphthyl acetate esterase and 5'-nucleotidase. This pattern differs from the zonal distribution of these cells seen in reactive lymphoid follicles. The nature and possible pathogenesis of AFLNH are discussed and contrasted with reactive hyperplasia.

5'-Nucleotidase

Pituitary adenomas producing growth hormone in acromegalic patients.

Growth hormone was shown in histological sections of 25 pituitary adenomas from acromegalic patients by means of the unlabelled peroxidase-antiperoxidase (PAP) technique. On the basis of the numbers of cytoplasmic granules, the cells of the adenomas were of two types: densely granulated and sparsely granulated. The densely granulated cells had abundant cytoplasm containing numerous granules, whereas the sparsely granulated cells had little cytoplasm with scanty granules. Depending on the predominant cell type the adenomas were also classified as densely granulated or sparsely granulated: 21 of the 25 adenomas (84%) were densely granulated and four (16%) sparsely granulated. There was some variation, however, in the relative numbers of the two types of cell from one part of an adenoma to another, a feature consistent with one type of cell in different phases of activity. There was no significant difference in mean serum growth hormone concentrations between the two groups, and granularity of the adenomas in histological sections did not therefore correlate with secretory activity. Nine adenomas showed extrasellar extension. The mean serum growth hormone concentration in these cases was lower than the mean of the adenomas confined to the sella turcica. Thus the size of the tumour did not correlate with the serum growth hormone concentration. Three of the four adenomas in the sparsely granulated group showed extrasellar extension, compared with 6 of 21 classified as densely granulated. This suggests that sparsely granulated adenomas have a more aggressive pattern of behaviour, but histological evidence for this was lacking.

Acromegaly

Study of nuclear sizes in the centres of malignant and benign lymphoid follicles.

The sizes of follicle centre cells in 15 specimens of follicular (centroblastic-centrocytic) non-Hodgkin's lymphoma and 15 specimens of reactive follicular hyperplasia have been measured. The findings differ from previous studies, where nuclei of cells from follicle centres and interfollicular areas were measured and revealed no significant difference between follicular lymphoma and reactive follicular hyperplasia. In the current study, by measuring only follicle centre cell nuclei, it has been found that, in reactive follicular hyperplasia, the mean nuclear maximum diameter (Dmax) and area are significantly greater than in centroblastic-centrocytic follicular lymphoma. In addition, the standard deviation of these data is greater for reactive follicular hyperplasia than follicular lymphoma, implying greater "scatter" or heterogeneity of the nuclear sizes in the follicle centre cells of the former than the latter. Thus, the size of these cells appears to be of value as an histological discriminator between these benign and malignant conditions.

Cell Nucleus

A comparative study of nuclear form factor, area and diameter in non-Hodgkin's lymphomas and reactive lymph nodes.

The mean nuclear area, maximum nuclear diameter (Dmax) and form factor (FF) have been measured in 30 specimens of non-Hodgkin's lymphoma (NHL) and 10 reactive lymph nodes, using the Reichert-Jung (Kontron) MOP-AMO3 image analyzer. Nuclear area and Dmax were found to be greater in high-grade NHL than in low-grade lymphomas and reactive nodes. In addition, there was close correlation between nuclear area and Dmax, especially for low-grade NHL and reactive specimens. As a means of distinguishing between high- and low-grade lymphomas, however, the FF appears to be of little value.

Cell Nucleus

The form factor of alpha-naphthyl acetate esterase-positive cells in non-Hodgkin's lymphomas and reactive lymph nodes.

The shape of alpha-naphthyl acetate esterase (ANAE)-positive cells (other than T lymphocytes) has been measured in 40 lymph nodes. The specimens comprised 15 high-grade lymphomas, 15 low-grade lymphomas and 10 reactive lymph nodes. The parameter used for the measurement of shape was form factor (FF), which is readily calculated by the Reichert-Jung (Kontron) MOP-AMO3 user-controlled image analyzer. Perfectly round cells have an FF value of 1.0, whereas the FF of irregularly-shaped cells diverges from unity. It has been demonstrated that the ANAE-positive cells in high-grade lymphomas have mean values for FF of 0.8-0.9, whereas in low-grade lymphomas and reactive nodes the mean value is 0.4-0.5. Thus, high-grade lymphomas contain many more rounded ANAE-positive macrophage type cells than do low-grade lymphomas and reactive nodes. In the latter two types of specimen there is an excess of branching and spindle-shaped ANAE-positive cells.

Carboxylic Ester Hydrolases

A quantitative study of the size of benign and malignant lymphoid follicles.

The mean areas of lymphoid follicles have been determined in 20 specimens of malignant follicular (centrocytic-centroblastic) lymphoma, 15 specimens of reactive follicular hyperplasia and 10 palatine tonsils. In all of the benign specimens and whenever possible for those showing malignancy, the areas of both the whole follicles (including the "mantle" zones) and of the follicle centres were measured; this procedure was facilitated by means of the Reichert-Jung (Kontron) MOP-AMO3 image-analyser. Reactive lymph nodes were found to have larger mean follicle areas than centrocytic-centroblastic lymphomas; the areas of reactive follicles also show greater variation than do those of their malignant counterparts. In addition, the "mantle" zone is usually absent from malignant follicles but may account for up to 65.5% of the mean total follicle size in reactive lymph nodes and tonsils.

Adolescent

A quantitative study of alpha-naphthyl acetate esterase-positive cells in non-Hodgkin's lymphomas and reactive lymph nodes.

The numbers of alpha-naphthyl acetate esterase (ANAE)-containing cells (other than T lymphocytes) in non-Hodgkin's lymphomas (NHL) and reactive lymph nodes have been counted, using the Reichert-Jung (Kontron) MOP-AMO3 user-controlled image analyzer. Twenty specimens of NHL and ten reactive nodes were examined. Cells were demonstrated by their content of acid alpha-naphthyl acetate esterase (ANAE) in fixed frozen sections. It was found that lymphomas of high-grade malignancy contained much larger numbers of ANAE-positive cells (10.8-20.5%) than those of low-grade malignancy (1.4-4.1%). The number of ANAE-positive cells (1.4-3.2%) in reactive lymph nodes was similar to that in low-grade NHL nodes.

Carboxylic Ester Hydrolases

A quantitative study of alpha-naphthyl acetate esterase-positive cells in Hodgkin's disease.

The numbers of alpha-naphthyl acetate esterase (ANAE)-positive cells (other than T cells) have been counted in 32 specimens of Hodgkin's disease and two specimens of histiocytic lymphoma. The different Rye subtypes of Hodgkin's disease contain varying numbers of enzyme-positive cells, ranging from 1.8-16% in the lymphocyte-predominant form to 39.8-47% in lymphocyte-depleted Hodgkin's disease. The percentage of enzyme-positive cells in the mixed cellularity variety was from only 6.5 to 14.6%. In the two specimens of apparently genuine histiocytic lymphoma, the enzyme-positive cells constituted 95.2 and 97.5% respectively of all cells. Thus, the numbers of macrophages and macrophage-like cells in true histiocytic lymphoma are much greater than in Hodgkin's disease.

Adolescent

Study of nuclear diameters in non-Hodgkin's lymphomas.

The mean maximum nuclear diameter (D(max)) in 21 cases of non-Hodgkin's lymphoma (NHL) has been determined, using the Reichert-Jung (Kontron) MOP-AMO(3) user-controlled image analyser. Nuclear diameters of high-grade malignancy NHL were found to be considerably greater than those of low-grade malignancy lymphomas, although there was some overlap of their ranges. These findings confirm objectively subjective estimates of nuclear size in NHL. The relative usefulness of the user-controlled (interactive) image analyser for the measurement of nuclei in tissue sections is compared with that of a fully automatic machine.

Cell Nucleus

Quantitative study of the immunoglobulin-containing cells in trephine samples of bone marrow.

Immunoglobulin (Ig) was demonstrated in paraffin sections of 12 trephine bone marrow biopsies by means of the unlabelled antibody peroxidase-antiperoxidase (PAP) method. The Ig-containing cells, which were counted with the Reichert-Jung (Kontron) MOP-AMO(3) user-controlled image-analyser, were found to constitute approximately 4.2% of all the nucleated cells in the marrow, a figure significantly higher than those reported by previous workers.

Bone Marrow

Effects of fixation and processing on immunohistochemical demonstration of immunoglobulin in paraffin sections of tonsil and bone marrow.

A number of fixatives were tested to determine their suitability for use with the unlabelled antibody peroxidase-antiperoxidase (PAP) method for demonstrating immunoglobulin in paraffin sections of tonsil and trephine samples of bone marrow. It was found that tonsil fixed in 'isotonic' solutions of formaldehyde reacted with the PAP method only after the sections had been trypsinised. Several other fixatives, including Bouin's fluid, Carnoy's fluid, and solutions containing mercuric chloride, gave tissues which reacted without trypsinisation of sections, and particularly good results were obtained with formol saline to which acetic acid (2-10%) had been added. A combination of acetic acid (10%)-formol saline and formol sublimate also gave excellent results with bone marrow. The influence on the PAP method of a number of steps in the processing of tissues and sections was also examined.

Bone Marrow

Intracellular filaments in human cancer cells: a histological study.

The distribution of intracellular filamentous systems in human breast and colonic cancers has been demonstrated by means of the tannic acid-phosphomolybdic acid-milling dye staining technique. Plasma membrane-associated staining is prominent in breast carcinomas and is strongest in anaplastic tumours. Strong staining is also noted in the cells at the margins of the tumours where the malignant cells are invading the surrounding tissues. In colonic carcinomas, filaments are mainly restricted to the terminal web region of the cells but dedifferentiation is accompanied by the development of circumferential staining of the cell membrane. The results are discussed in relation to immunohistochemical and electron microscopic studies of contractile proteins in non-muscle cells.

Adenocarcinoma

Non-Hodgkin's lymphomas: an immunohistochemical and histological study.

Immunohistochemical and histoogical studies have been performed on paraffin sections of 19 cases of non-Hodgkin's lymphoma (NHL). All the cases were lymphocytic in type and, on the basis of the National Lymphoma Investigation classification, 11 were follicular (six small, three mixed small and large, and two large cell types) and eight were diffuse (four intermediate, three poorly and one well-differentiated types). Marshall's metalophil method revealed a population of dendritic histiocytes in and around the follicles of follicular lymphomas. The distribution of the dendritic cells within the neoplastic follicles resembled the distribution of similar cells in reactive follicles, lending support to the concept of an origin for lymphoma follicles from their reactive counterparts. In the diffuse lesions the dendritic cells were large and more pleomorphic than in the follicular lesions, but these features were not so pronounced as those previously observed in Hodgkin's disease. The PAP sequence was used to demonstrate Ig, and as judged by the types of light and heavy chains in the lymphoma cells, the cases were divided into three groups: Group 1 (eight cases) in which the lymphoma cells contained monotypic Ig; Group 2 (six cases) in which monotypic Ig was probably present; and Group 3 (four cases) where no evidence of monotypic Ig secretion was found. Monotypic Ig was most commonly found in follicular lymphomas, mu kappa secretion being the most frequently identified combination of heavy and light chains. The majority of cases (73 per cent.) were thus clearly derived from B lymphocytes. However, the fact that monoclonality was evident in only a proportion of cases suggested that lymphomas may be polyclonal initially and proportion of cases suggested that lymphomas may be polyclonal initially and that monoclonality is a later development. In addition to the lymphoma cells, normal mature plasma cells containing a high concentration of intracellular Ig were present in all but one of the lesions. The Ig was polytypic, cells containing kappa and lambda chains being present in roughly equal numbers and gamma chains pre-dominating. Extracellular Ig (gamma, mu, kappa, lambda) was also present in many lesions. Collections of small non-lymphomatous lymphocytes were also present in all cases. In eight lesions these appeared to have polytypic surface Ig (mu, kappa, lambda). Dendritic cells mingled with these lymphocytes. Collections of small lymphocytes non-reactive for Ig were also present. These had no association with dendritic histiocytes and might have been T cells. It is concluded that in most cases immunohistochemistry alone provides an insufficient basis for the diagnosis of lymphoma and that disturbance of cellular morphology and tissue architecture remain the most useful criteria on which the diagnosis of lymphoma rests.

Adult

A study of nuclear diameters in lymph node imprints using the Zeiss Microvideomat.

The diameters of the cell nuclei were measured in imprint preparations of eight tonsils and 28 lymph nodes, each specimen being from a separate patient. The lymph nodes were from cases of Hodgkin's disease (HD), non-Hodgkin's lymphoma (NHL), and reactive benign states. The nuclear diameters were measured by means of an image-analysing device, the Zeiss Microvideomat. For accurate measurements, the cells had to be well separated, and tissue sections could not be used because the close juxtaposition of nuclei gave erroneous readings. However, cell imprints proved suitable. The results show that the mean nuclear diameters for the HD, NHL, and reactive groups differ and show a considerable scatter. However, the distributions for the NHL and reactive nodes are sufficiently different to suggest that the method may have diagnostic value for the former.

Adolescent

Identification of myosin in human epithelial cancers with immunofluorescence.

The location of myosin in neoplastic cells from human breast, colonic, gastric, bronchial, skin, esophageal, and renal carcinomas has been examined using an immunofluorescence technique with an antibody raised against human smooth muscle myosin. Normal tissues and fibroblast cell cultures were also investigated. In all the tumors myosin was located in the cytoplasm adjacent to the plasma membrane. Cancer cells appeared more strongly immunofluorescent than normal tissues. The precise pattern of immunofluorescence in neoplastic cells varied with the histologic type of the tumor. Linear immunofluorescence around the outer border of the cytoplasm was the most common pattern observed, but in well differentiated adenocarcinomas, myosin was located chiefly in relation to the microvillous border. In three of the squamous carcinomas a granular pattern of immunofluorescence was observed. Undifferentiated breast carcinomas did not contain more myosin than better differentiated tumors, and the intensity of immunofluorescence was no greater in invasive cancer cells than noninvasive tumor cells. The results suggest that myosin is present in greater amounts in neoplastic cells than normal cells and may be concerned with cell shape and polarity as well as cell movement.

Animals

Hodgkin's disease: an immunohistochemical and histological study.

The distribution of immunoglobulin (Ig) in Hodgkin's tissue has been demonstrated in paraffin and cryostat sections by the unlabelled antibody peroxidase-antiperoxidase (PAP) method and the two-stage fluorescein isothiocyanate (FITC)-based technique. The morphology and histogenesis of the Reed-Sternberg (RS) and Hodgkin (HD) cells has been studied with the metalophil method of Marshall (1948) and this revealed a population of dendritic histiocytes which corresponded in number, sizes and distribution to the RS and HD cells in adjacent sections stained by haematoxylin and eosin. The largest RS cells, however, appeared to be non-dendritic. A notable feature of Hodgkin's tissue was the tendency for the dendritic cells to form "nodules", in combination with a population of small lymphocytes. The PAP technique reveals Ig in the form of mu and delta heavy chains, as well as kappa and lambda light chains, in close association with and probably on the surface of a high proportion of these lymphocytes, suggesting that they are immature B cells. Similar reactions were given by the mantle of lymphocytes of surviving normal lymphoid follicles, and metalophil dendritic histiocytes were also demonstrated within the mantle and subjacent part of the germinal centre. Numerous immunocytes containing Ig were present in all lesions; in the majority of cases, more cells contained gamma than alpha or mu heavy chains, although in these cases alpha-positive cells outnumbered those containing gamma or mu heavy chains. In two-thirds of the cases, one-third of the RS cells contained cytoplasmic immunoglobulin. This was exclusively gamma heavy, although both light chains were present. In about half the cases a minority of the HD cells contained gamma chain. The results suggest that HD and RS cells are dendritic histiocytes of the type normally found in the lymphoid follicles and that their tendency to form nodules in assoication with B lymphocytes is a manifestatin of this origin. It is suggested that the presence of Ig most probably results from absorption of antigen-antibody complexes on the cell surface.

Adolescent

Immunoglobulin in Reed-Sternberg and Hodgkin cells.

In eight cases of Hodgkin's disease of various types, Ig was found within approximately one-third of the RS and HD cells. The Ig within each RS and HD cell consisted of gamma heavy chains and both k and lambda light chains. The most probable origin of the Ig would appear to be uptake of IgG-containing immune complexes. The presence of both types of light chain in individual RS and HD cells is inconsistent with an origin of these types of cell from B lymphocytes.

B-Lymphocytes