X-ray detectable thread for orientating a breast specimen--an affordable and less cumbersome solution.
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Breast Diseases↗
Biomedical subjects
J C Macartney
Publications and source records attributed to J C Macartney.
Germinal-center cell proliferation in response to T-independent antigens: a stathmokinetic, morphometric and immunohistochemical study in vivo.
Although the nature of the germinal center reaction during responses to T-dependent antigens has been well documented, much less is known regarding the relationship between germinal centers and T-independent antigens. In this study, germinal-center cell proliferation was determined at specific time points in spleens of C3H/HeN mice following immunization with either the type-1, T-independent antigen dinitrophenol-lipopolysaccharide (DNP-LPS), or the type-2, T-independent antigen DNP-Ficoll. A stathmokinetic technique was employed to assess proliferation in terms of germinal center cell birth rate and morphometry was used to measure actual growth and regression of the germinal center cell population. An estimate of the absolute rate of germinal-center (GC) cell proliferation was derived from these two values. In addition, immunohistochemistry was performed to correlate changes in GC cell proliferation with the presence or absence of antigen within GC. Following immunization with both antigens, there was an initial reduction of proliferation within pre-existing germinal centers which manifested as either GC dissociation (DNP-LPS) or a suppression of birth rates (DNP-Ficoll). This was followed by a period of increased GC cell proliferation in animals immunized with DNP-LPS, but not in those exposed to DNP-Ficoll. GC cell proliferation was then measured in mice treated with cyclosporin A from 1 day before to 2 days after immunization with DNP-LPS. In these animals, the expected increase in GC cell birth rates did not take place. Immunohistochemistry showed that DNP-Ficoll and DNP-LPS were present in GC from 1 day after immunization until the end of the experiment on day 7. Treatment with cyclosporin A did not affect the deposition of DNP-LPS in GC. These results show that only some T-independent antigens are able to stimulate GC cell proliferation, and we propose that this is related to their ability to recruit precursors of GC B cells into the GC reaction. In addition, the results indicate that GC proliferation seen in response to a so-called T-independent antigen is at least partly driven by T cell-derived cytokines.
Animals↗
Regulation of murine germinal centre cell proliferation in vivo: a stathmokinetic study examining the effect of differently timed doses of cyclosporin A.
Although studies have identified factors which affect germinal centre cell proliferation in vitro, their relative contributions in vivo remain largely undetermined. In this study, the proliferative rate of germinal centre cells was measured in sheep red blood cell-immunized C3H/HeN mice exposed to variously timed doses of cyclosporin A. Germinal centre (GC) cell proliferation was measured by a stathmokinetic technique to determine GC cell birth rates at specific time points after immunization. Changes in total GC volume were determined by morphometry in order to assess actual growth and regression of the GC cell population. An estimate of the absolute rate of GC cell proliferation was derived from these two values. Following exposure to antigen, there was an initial inhibition of proliferation within pre-existing germinal centres, followed by a rapid rise, then a sustained phase of increased GC cell proliferation. By comparing the effects of the different cyclosporin A treatment regimes, it was possible to deduce that the initial inhibition of proliferation was mediated by a T-cell-derived cytokine, as was the final sustained phase of the proliferative response. The intervening rise in GC cell proliferation, however, was attributable to a contact-dependent signalling mechanism.
Animals↗
Reduced apoptotic cell death in follicular lymphoma.
It has been hypothesized that inhibition of germinal centre cell apoptosis may underlie the development of follicle centre cell lymphomas. We have performed a comparative, quantitative study of apoptotic cell death in germinal centres and in the neoplastic follicles of centroblastic-centrocytic, follicular, non-Hodgkin's lymphoma (Cb/Cc NHL). Ten cases each of reactive follicular hyperplasia and Cb/Cc NHL were analysed. One-micrometre-thick resin-embedded sections were examined at x 1000 magnification. The total numbers of cells, nuclear containing apoptotic bodies, and mitoses were counted in each follicle and the apoptotic and mitotic indices were derived. Transmission electron microscopy was performed on selected cases to confirm the typical features of apoptosis. The mean apoptotic (4.9 per cent) and mitotic indices (0.9 per cent) for the germinal centres were significantly higher (P much less than 0.001) than those for the neoplastic follicles (0.9 and 0.14 per cent). These results lend support to the recent proposal that reduced apoptotic cell death may be important in the pathogenesis of follicular lymphomas.
Cell Survival↗
Cell kinetics of human gastric mucosa and gastric cancer in organ culture.
The cell kinetics of human gastric epithelium in organ culture have been measured using flash labelling with tritiated thymidine and the metaphase arrest technique to estimate cell birth rates. Normal gastric antral and body mucosa have been compared with mucosa showing gastritis and gastric carcinoma. Labelling indices with tritiated thymidine in normal gastric mucosa declined over a 48-h period suggesting that essential growth factors were lacking. Labelling indices and cell birth rates were higher in gastritis than in normal mucosa and highest in gastric carcinoma. Labelling indices were higher in intestinal-type gastric carcinoma than diffuse carcinoma. In metaphase arrest experiments carcinomas showed on average an eightfold increase in resistance to the metaphase-arresting properties of vincristine when compared with normal mucosa. The validity of using the metaphase arrest technique to measure cell birth rate in gastric cancers in view of this vincristine resistance is discussed.
Cell Cycle↗
DNA flow cytometry of follicular non-Hodgkin's lymphoma.
S-phase fraction, an index of cellular proliferation, and DNA ploidy were measured by DNA flow cytometry in a retrospective study of lymph node biopsy specimens from 83 cases (before treatment) of follicular non-Hodgkin's lymphoma, Working Formulation categories B and C. The correlations between these measures and survival, clinical stage, symptoms and histopathological factors were investigated. Aneuploidy was rare (n = 16) and had no effect on length of survival or transformation to high grade lymphoma. The overall mean S-phase fraction was 3.6%; for the whole series increasing S-phase fraction was associated with decreased survival. A high S-phase fraction (more than 5%) in initial biopsy specimens was also associated with an increased risk of subsequent high grade transformation at relapse. There was no difference between the survival or proliferative activity of tumours composed of mainly small cleaved cells compared with those composed of mixed small and large cells. There was no difference in survival or proliferative activity between tumours showing a pure follicular growth pattern and those with a mixed follicular and diffuse growth pattern. Multifactorial analysis showed that an S-phase fraction of more than 5% and B symptoms were the most important factors determining survival in these follicular non-Hodgkin's lymphomas.
Adult↗
DNA flow cytometry of non-Hodgkin's lymphomas.
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DNA, Neoplasm↗
Adenoidal hypertrophy as the presenting feature of HIV infection.
A case of symptomatic recurrent adenoidal hypertrophy, as the presenting feature of HIV infection in a haemophiliac child, is reported. The incidence of non-malignant nasopharyngeal lymphoid hyperplasia in HIV infection is examined and the relevance of the histological appearance is discussed in relation to progression of disease.
Adenoids↗
Differential upregulation of intercellular adhesion molecule-1 in coeliac disease.
The expression of intercellular adhesion molecule-1 (ICAM-1) was studied on peroral jejunal biopsies from patients with coeliac disease. The biopsies from untreated patients exhibited greater staining of the superficial lamina propria cells compared with treated patients and controls. A gluten challenge in treated patients produced an altered staining pattern within 2 h. The results demonstrate the role of ICAM-1 expression in coeliac disease, providing further evidence for the role of lamina propria cells in the pathogenesis of this condition.
Antigens, CD↗
Measurement of S-phase fractions in lymphoid tissue comparing fresh versus paraffin-embedded tissue and 4',6'-diamidino-2 phenylindole dihydrochloride versus propidium iodide staining.
S-phase fractions for 62 lymphoid biopsies were calculated, by means of flow cytometry, from both fresh and paraffin-embedded tissue. The purposes of this study were to determine whether significant differences were seen between S-phase estimates obtained from fresh and fixed tissue and to compare results obtained with two DNA dyes, namely 4'-6'-diamidino-2 phenylindole dihydrochloride (DAPI) and propidium iodide (PI). The 62 cases consisted of 38 cases of non-Hodgkin's lymphoma (NHL), 19 reactive samples, and 5 cases of Hodgkin's disease. Fifty-four of the samples showed DNA diploid profiles. A good agreement between S-phase results from fresh and fixed tissue was seen, with technical factors accounting for around 20% of the total variance. Using a paired t test, no significant difference was seen between fresh and fixed tissue for diploid cases, but there was a trend for S-phase estimates from fixed tissue to be higher. If all cases (including the eight DNA aneuploid samples) were included in the analysis this difference just reached statistical significance (P less than .05). In a subgroup of 19 of the cases, a comparison was performed on both fresh and fixed tissue of staining with DAPI and PI. A good agreement between results with both DNA stains was found on fresh and fixed tissue, with no significant differences being apparent, and stain-related factors accounted for only 10% of the total variance.
Cell Cycle↗
DNA flow cytometry of thymomas.
Forty-seven thymomas have been examined by DNA flow cytometry and results correlated with histology, stage, associated clinical features and survival. Twenty-five cases were DNA diploid, 14 were aneuploid and no results could be obtained for eight cases. The presence of aneuploidy correlated with more advanced (stage II and III) disease and the presence of myasthenia gravis and was more frequent in epithelial predominant thymomas. Tumour recurrence was more frequent in DNA aneuploid tumours, stage II/III disease and epithelial predominant neoplasms. Multifactorial analysis showed that DNA aneuploidy was predictive of tumour recurrence independent of the effects of stage and histology.
Adult↗
Correlation between DNA flow cytometric and nucleolar organizer region data in non-Hodgkin's lymphomas.
The argyrophilic staining (AgNOR) technique, novel in histopathology, was applied to a series of 20 non-Hodgkin's lymphomas (NHL) of established Kiel subtype. The method demonstrates nucleolar organizer regions (NORs) by virtue of sulphydryl groups on their associated proteins and the enumeration of AgNOR foci has been previously shown to discriminate between NHL of low- and high-grade histological types. This finding was confirmed and the results were compared with those obtained by means of DNA flow cytometry performed on paraffin wax-embedded tissue from the same lymphomas. There was a very good linear correlation between the mean numbers of AgNOR sites per nucleus and the percentage of S-phase cells for each case, both values being high in high-grade NHL and low in low-grade lesions. Conversely there was no significant correlation between the DNA index, representing DNA aneuploidy, and AgNOR counts. It is suggested that the numbers of AgNORs in a lymphoma may be related to the dividing fraction of cells rather than, as might be expected, to ploidy alone. It is also proposed that the AgNOR technique, which is rapid, simple, and inexpensive, may provide, at least, an adjunct to DNA flow cytometry in the assessment of neoplasm in histopathology.
Cell Count↗
Proliferative activity in lymphomas.
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Cell Division↗
A comparison of in vitro and in vivo gastric mucosal cell kinetics.
In order to determine whether organ culture of gastric mucosa preserves in vivo kinetic alterations, a comparison of in vivo and in vitro measurements of cell proliferation was made on antral mucosa from rats treated with the carcinogen methyl-nitro-nitrosoguanidine, administered orally for up to 30 weeks. Morphologic, morphometric and cell kinetic features in gastric mucosa were observed in vivo in treated and control rats. Similar in vitro measurements were made on mucosa from treated and control rats after a further 24-hour organ culture. All carcinogen-treated stomachs showed erosions, with widespread areas of glandular architectural irregularity which were more widespread after 30 weeks carcinogen treatment. Organ cultures showed good preservation of these morphologic features. In areas of architecturally normal mucosa, the carcinogen caused an increase in antral pit vertical column counts. This alteration was preserved after organ culture of carcinogen-treated mucosa. Cell birth rates and [3H]thymidine flash labeling indices were raised in architecturally normal mucosa from carcinogen-treated animals. These kinetic indices continued to be elevated after organ culture, though the in vitro values were lower than in vivo. Cell birth rates in architecturally abnormal mucosa from carcinogen-treated animals did not differ significantly from adjacent morphologically normal mucosa. Despite evidence of epithelial cell loss with depression of kinetic activity on organ culture compared with in vivo results, organ culture gives consistent results which reflect methyl-nitroso-nitrosoguanidine-induced changes and is of value for further in vitro investigations.
Animals↗
Expression of c-myc in non-malignant and pre-malignant gastrointestinal disorders.
A monoclonal antibody 1-6E10 against the protein product p62c-myc of the c-myc oncogene was used to assess, by immunohistology, a variety of non-neoplastic and preneoplastic disorders of gastric and colonic mucosa. There were low levels of expression of the c-myc oncogenic product in normal gastric and colonic tissue. In gastric mucosa, increased expression was observed with inflammatory, metaplastic and dysplastic histological appearances. In the normal colon low levels of expression were observed, but there was increased expression in inflammatory disorders including Crohn's disease and ulcerative colitis. There was also increased expression in colonic dysplasia associated with ulcerative colitis. The oncogene product was localized in the cytoplasm, nuclei and Golgi apparatus. C-myc 1-6E10 may therefore be used as a marker to identify the cellular proliferative response in gastric and colonic mucosa that is associated with inflammation as well as potentially neoplastic hyperproliferative states.
Antibodies, Monoclonal↗
Fucose-containing antigens in normal and neoplastic human gastric mucosa: a comparative study using lectin histochemistry and blood group immunohistochemistry.
The histochemical binding to normal and neoplastic human gastric mucosa of two lectin-peroxidase conjugates which are specific for fucose-containing glycoconjugates is described. The lectins are Ulex europaeus (UEA1) and Lotus tetragonolobus (LTA). Results are compared with ABO and secretor status and the immunohistochemical demonstration of a Type 1 antigen (Lewisa) and two Type 2 antigens (X and H) using monoclonal antibodies. Binding of UEA 1 and LTA to surface mucus cells in normal gastric mucosa is only seen in secretors but is independent of ABO status. In gastric carcinomas lectin binding is reduced. There is a relationship between UEA1 binding and the immunohistochemical demonstration of H Type 2 antigen and secretor activity. In contrast LTA staining is associated with both H Type 2 and Lea antigen but not with secretor status. X antigen is only demonstrable in small amounts. Despite subtle differences in the binding patterns of the two lectins, immunohistochemical studies with monoclonal antibodies against defined oligosaccharides provide greater information. The results of the study are consistent with the hypothesis that competitive interaction between fucosyl and sialyl transferases occurs in gastric malignancy and leads to the expression of abnormal blood group-related antigens.
ABO Blood-Group System↗
Timing of infiltration of T lymphocytes induced by gluten into the small intestine in coeliac disease.
Jejunal biopsy was performed on control subjects and patients with treated and untreated coeliac disease. Monoclonal antibodies to T lymphocyte surface markers were used to quantify T cell phenotypic subsets in the jejunal mucosa. The patients with untreated coeliac disease had significantly more of both suppressor/cytotoxic and helper/inducer T cells in the surface epithelium than either the control subjects or the treated patients. Serial jejunal biopsy specimens were taken from five treated coeliac patients for six hours after a gluten challenge. In four of these five infiltration of the surface epithelium by both T cell phenotypes, together with deterioration in the villus architecture, had occurred both within two hours of having started the challenge. This suggests that T lymphocytes may have a role in the pathogenesis of coeliac disease.
Adolescent↗
HLA-DR, DP and DQ expression in the small intestine of patients with coeliac disease.
Frozen sections of jejunal mucosa from control subjects and patients with both treated and untreated coeliac disease were examined for HLA class II DR, DP and DQ expression. Different staining patterns with monoclonal antibodies to the different class II subgroups were observed with the control subjects. There was some inter-subject variation but in general DR greater than DP greater than DQ staining was observed with the villous enterocytes staining most strongly with the staining decreasing towards the crypt bases. The patients with treated coeliac disease gave a similar pattern to the controls. The patients with untreated coeliac disease generally gave a more intense and relatively uniform staining of both surface and crypt enterocytes for all class II subgroups.
Celiac Disease↗