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Biomedical subjects

J Crocker

Publications and source records attributed to J Crocker.

At least 73 records · Page 4Linked to original sources
PubMed1994

p53, c-myc p62 and proliferating cell nuclear antigen (PCNA) expression in non-Hodgkin's lymphomas.

AIMS: To investigate the immunohistochemical expression of p53 protein in non-Hodgkin's lymphomas (NHL) and its relation to that of c-myc p62 oncoprotein and proliferating cell nuclear antigen (PCNA). METHODS: Paraffin wax embedded tissue from 90 non-Hodgkin's lymphomas (72 B cell and 18 T cell) was stained immunohistochemically for p53 protein, c-myc p62 oncoprotein, and PCNA using the monoclonal antibodies DO7, c-myc 1-9 E10, and PC-10, respectively. RESULTS: Of the non-Hodgkin's lymphomas studied, 55 (61%) stained positively for p53 protein. The proportion of positive cases increased from low grade non-Hodgkin's lymphoma and was higher in tumours of T cell origin. The percentage of positive cells (labelling index or LI) was significantly lower in low grade non-Hodgkin's lymphoma, but no difference was established between intermediate and high grade non-Hodgkin's lymphoma. In a large proportion of low grade non-Hodgkin's lymphoma the LI was below 1%. c-myc p62 immunoreactivity was identified in all cases. A significant positive correlation was established between p53 LI and c-myc p62 LI (rs = 0.453) as well as between p53 LI and PCNA LI (rs = 0.338). CONCLUSIONS: p53 immunoreactivity was present in about half the cases of non-Hodgkin's lymphoma and was related to the grade of malignancy and possibly to the B or T cell origin of the tumour. It was also associated with the proliferation state as expressed by PCNA LI and c-myc p62 expression, indicating that the expression of these three cell cycle-related genes might be interrelated.

Antibodies, Monoclonal↗
PubMed1993

Epstein-Barr virus and Hodgkin's disease: transcriptional analysis of virus latency in the malignant cells.

Epstein-Barr virus (EBV) is associated with a number of different human tumors and appears to play different pathogenetic roles in each case. Thus, immunoblastic B cell lymphomas of the immunosuppressed display the full pattern of EBV latent gene expression (expressing Epstein-Barr nuclear antigen [EBNA]1, 2, 3A, 3B, 3C, and -LP, and latent membrane protein [LMP]1, 2A, and 2B), just as do B lymphoblastoid cell lines transformed by the virus in vitro. In contrast, those EBV-associated tumors with a more complex, multistep pathogenesis show more restricted patterns of viral gene expression, limited in Burkitt's lymphoma to EBNA1 only and in nasopharyngeal carcinoma (NPC) to EBNA1 and LMP1, 2A, and 2B. Recent evidence has implicated EBV in the pathogenesis of another lymphoid tumor, Hodgkin's disease (HD), where the malignant Hodgkin's and Reed-Sternberg (HRS) cells are EBV genome positive in up to 50% of cases. Here we extend preliminary results on viral gene expression in HRS cells by adopting polymerase chain reaction-based and in situ hybridization assays capable of detecting specific EBV latent transcripts diagnostic of the different possible forms of EBV latency. We show that the transcriptional program of the virus in HRS cells is similar to that seen in NPC in several respects: (a) selective expression of EBNA1 mRNA from the BamHI F promoter; (b) downregulation of the BamHI C and W promoters and their associated EBNA mRNAs; (c) expression of LMP1 and, in most cases, LMP2A and 2B transcripts; and (d) expression of the "rightward-running" BamHI A transcripts once thought to be unique to NPC. This form of latency, consistently detected in EBV-positive HD irrespective of histological subtype, implies an active role for the virus in the pathogenesis of HD and also suggests that the tumor may remain sensitive to at least certain facets of the EBV-induced cytotoxic T cell response.

Antigens, Viral↗
PubMed1993

A simple technique for the measurement of fractal dimensions in histopathological specimens.

A computer program has been devised which enables a simple method for the fractal dimension analysis of histological or cytological material to be performed rapidly with relatively inexpensive hardware. The fractal dimension of a structure refers to its self-similarity over a range of scales and appears to be well suited to histopathological preparations. Thus, the fine 'roughness' of object profiles can be assessed more appropriately by this technique than by means of conventional Euclidean geometry. Images of the object(s) to be investigated are firstly digitized after presentation to a high-performance computer via a video camera or a graphics tablet system and then analysed using the computer program, which has its basis in a standard perimeter estimate method. It is proposed that such techniques may find extensive use in investigative and diagnostic histopathology.

Anthropometry↗
PubMed1993

The effect of different fixatives and length of fixation time on subsequent AgNOR staining for frozen and paraffin-embedded tissue sections.

The AgNOR technique has been used extensively in studies investigating the possibility that the numbers and appearances of the intranuclear structures stained are markers of malignancy. The method has the advantage of being applicable to many different types of histological material, including paraffin-embedded tissue. However, it has been suggested that the visualization of AgNORs is dependent on the type and time of fixation employed. This study set out to measure this effect with the following commonly-used fixatives: acetone, absolute ethanol, methanol, Carnoy's fluid, Bouin's fluid, 4% glutaraldehyde, 10% neutral buffered formalin and 10% formol-saline. Both frozen sections and blocks of fresh tonsil were fixed for varying times, the blocks of tissue then being processed routinely. With the frozen sections AgNORs were easier to discern than in sections of paraffin-embedded tissue, and more intranucleolar AgNORs were visible when alcoholic fixatives were used than with aldehyde fixation. The effects of different fixatives on AgNOR appearance in paraffin sections is, however, more complex. Despite the variation caused by different fixatives, AgNORs could be demonstrated adequately with all the fixatives studied. It is concluded that fixation is not a limitation to the study of AgNORs provided that the time and type of fixative is controlled.

Acetates↗
PubMed1993

The stigma of overweight: affective consequences of attributional ambiguity.

Attributing negative outcomes to prejudice and discrimination may protect the mood and self-esteem of some stigmatized groups. Thus, the overweight may be low in self-esteem because they blame their weight, but not the attitudes of others, for negative outcomes based on their weight. In an experiment, 27 overweight and 31 normal weight college women received either positive or negative social feedback from a male evaluator. Relative to other groups, overweight women who received negative feedback attributed the feedback to their weight but did not blame the evaluator for his reaction. This attributional pattern resulted in more negative mood for these overweight women in comparison with other groups. Dimensions of stigma that may account for differences in the tendency to attribute negative outcomes to prejudice, and implications of these findings for weight loss programs and psychotherapy for the overweight, are discussed.

Adult↗
PubMed1993

Ependymal cells of the choroid plexus express tumour necrosis factor-alpha.

Tumour necrosis factor-alpha (TNF alpha) is a major proinflammatory cytokine which appears in the cerebrospinal fluid very early after endotoxin challenge, and is likely to be produced locally. Following in vivo and in vitro challenge with endotoxin, we have demonstrated immunocytochemically and by in situ hybridization that pig and guinea-pig choroid plexus ependymal cells can produce TNF alpha. Immuno-electron microscopy shows that this protein is localized within ependymal cells to the cytoplasm and microvilli. We suggest that this TNF alpha may be important in the initiation of the inflammatory response in bacterial meningitis.

Animals↗
PubMed1993

Correlation between PCNA and AgNOR scores in non-Hodgkin's lymphomas using sequential staining technique.

AIMS: To investigate the relation between the numbers of interphase silver stained nucleolar organiser regions (AgNORs) and immunolabelling with the monoclonal antibody PC10, which demonstrates proliferating nuclei by reacting with proliferating cell nuclear antigen (PCNA). METHODS: The established sequential technique for the demonstration of interphase AgNORs and of antigens in paraffin wax sections was applied to a small series of non-Hodgkin's lymphomas (NHL) of both low and high grade type, together with specimens of palatine tonsil. The numbers of PCNA positive cells were counted in all specimens; in the tonsils the cells were counted in both follicle centres and in the interfollicular areas. The numbers of AgNORs in both PCNA positive and PCNA negative nuclei were then counted. RESULTS: Lower numbers of PCNA positive cells were found in the low grade than the high grade NHL (18-28.4% and 34.2-51.3%, respectively). This was reflected in the two areas of the palatine tonsils, the counts being higher in the follicle centre nuclei than in those in the interfollicular compartments. In general, the numbers of AgNORs were higher in the PCNA positive nuclei than in those lacking the antigen; however, a consistent finding was that relatively high AgNOR scores were observed in PCNA negative nuclei, especially in the high grade lymphomas. In the tonsils, however, the AgNOR counts were much lower in the nuclei lacking PCNA than in those containing it. CONCLUSIONS: The results obtained in the lymphomas were rather unexpected as, in general, previous studies have shown a close direct or indirect relation between AgNOR scores and proliferating cell counts. An explanation for these findings may be that the argyrophil proteins associated with proliferating cells remain in the nucleus in detectable form longer than the PCNA antigen, at least in neoplastic tissue.

Antigens, Neoplasm↗
PubMed1993

p53 expression in oat and non-oat small cell lung carcinomas: correlations with proliferating cell nuclear antigen.

AIMS: To investigate the immunohistochemical expression of p53 protein in small cell lung carcinoma (SCLC), comparing it with that in non-small cell carcinoma (NSCLC); and to evaluate the correlation between p53 and proliferating cell nuclear antigen (PCNA) expression as well as between p53 and PCNA expression and survival. METHODS: Paraffin wax embedded tissues from 61 cases of primary lung carcinoma were stained for p53 protein and PCNA using the monoclonal antibodies 1801 and PC-10, respectively, in a standard avidin-biotin immunoperoxidase method. RESULTS: Of the 61 lung carcinomas 35 (57%) were positive for p53 (range 1% to 90%). Ninety percent of the non-oat SCLC contained positive cells and the labelling index (LI) was significantly higher than that of the oat SCLC (p < 0.001). SLCC also displayed a higher p53 LI than NSCLC (p < 0.01); no difference was found between squamous carcinoma, adenocarcinoma, and oat cell carcinoma. A p53 LI of greater than 1% tended to be associated with nodal metastases (p < 0.05), and p53 expression in node positive tumours as well as in oat cell carcinomas was indicative of poorer survival (p < 0.01 and p < 0.1, respectively). A p53 Li of greater than 60% was a negative prognostic factor in non-oat SCLC (p < 0.05). PCNA LI was highest in non-oat SCLC and lowest in NSCLC; oat cell carcinomas had a mean LI intermediate between NSCLC and non-oat SCLC (NSCLC v oat cell carcinoma p < 0.05 and oat cell v non-oat cell carcinomas p < 0.01). A PCNA LI was not correlated with nodal metastases or survival, but there was a significant positive correlation between PCNA LI and p53 LI (rs = 0.484, p < 0.001). CONCLUSIONS: p53 and PCNA expression differ substantially among the various types of lung carcinomas. Substantial differences were also found between oat and non-oat types of SCLC, indicating that SCLC is heterogeneous as far as proliferation rate and altered p53 expression is concerned. p53 seems to be of some prognostic value. The relation between PCNA and p53 expression indicates that the PCNA gene is slightly upregulated by p53.

Antigens, Neoplasm↗
PubMed1993

Proliferating cell nuclear antigen (PCNA) and nucleolar organiser regions in Hodgkin's disease: correlation with morphology.

AIM: To define the distribution of proliferating cell nuclear antigen (PCNA) and silver staining nucleolar organiser regions (AgNORs) in Hodgkin's disease. METHODS: PCNA was shown in a series of 34 cases of Hodgkin's disease using immunohistochemical methods. In a second series of 46 cases the AgNOR technique for interphase nucleolar organiser regions was studied. Both series comprised routinely fixed and processed paraffin wax sections of three main Rye subtypes. RESULTS: In all cases, regardless of Rye subtype, most Sternberg-Reed cells and mononuclear Hodgkin cells showed nuclear PCNA immunoreactivity and such cells had 15 or more AgNOR sites. The Hodgkin cells had, in general, about half the number of AgNORs seen in Sternberg-Reed variants. CONCLUSIONS: These data support the notion that Hodgkin's disease can be regarded as a high grade lymphoma, the large Hodgkin's and Sternberg-Reed cells being the (PCNA positive and AgNOR rich) neoplastic elements with high proliferative capacity. A smaller proportion of the associated cells also showed evidence of proliferation.

Antigens, Neoplasm↗
PubMed1993

Would people with a disability in the highlands benefit from a community-based rehabilitation program?

Community-based rehabilitation for those people with a physical disability is a policy promoted by the World Health Organization. In order to assess whether such a program might be useful to the disabled people of the highlands of Papua New Guinea a survey was conducted which first identified those people with a severe physical disability and then investigated the degree that they were handicapped in terms of their social and physical environment. The survey was performed in the Tari area of the Southern Highlands Province in conjunction with the Papua New Guinea Institute of Medical Research (PNGIMR). By using the PNGIMR demographic surveillance system it was possible to calculate a prevalence level of physical disability (including walking disability, deafness and blindness) of 46 per 10,000 (0.46%). A significant physical disability was identified in 114 people, of whom 54 were given personal interviews to establish their quality of life. The survey found the social and economic situation of disabled people to be generally good although there is a lack of basic material aids for handicapped people. The disabled people and their families do not need extra knowledge about how to care for their disabilities and a formal community-based rehabilitation program would be inappropriate, but they would find mobility aids such as wheelchairs and artificial limbs of enormous help. The regular health care services are widely used although both people with a disability and health service staff are not always aware of the types of treatment which can usefully be provided.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

The induction by human interleukin-6 of apoptosis in the promonocytic cell line U937 and human neutrophils.

Apoptosis of neutrophils at sites of inflammation in vivo is thought to lead to their recognition and safe elimination by macrophages. Little is known, however, about the regulation of apoptosis in myeloid cells. We report here that the human promonocytic leukemic cell line, U937, and mature human neutrophils can be induced to become apoptotic when cultured with interleukin-6. Apoptosis of U937 cells, assessed morphologically and by the presence of DNA fragmentation, was increased significantly in a dose-dependent fashion by concentrations of 0.5-100 ng/ml interleukin-6. Apoptosis of U937 cells was evident after 48 h of incubation with 20 ng/ml interleukin-6, and the effect was eliminated by adsorption of interleukin-6 with a specific monoclonal antibody. Apoptosis was not evident in the presence of the differentiating agent phorbol 12-myristate 13 acetate; the induction of apoptosis in U937 cells was not therefore a consequence of differentiation. Apoptosis of mature neutrophils was enhanced after 24 h in culture with interleukin-6. Interleukin-6 might be an important factor in the normal resolution of inflammation through the induction of apoptosis of neutrophils.

Antibodies, Monoclonal↗
PubMed1992

Patterns of Epstein-Barr virus infection in non-neoplastic lymphoid tissue.

Taking advantage of the abundant expression of the small Epstein-Barr virus (EBV)-encoded RNAs (EBERs) in latently infected cells, we have analyzed 72 normal and hyperplastic lymph nodes and three tonsils of acute infectious mononucleosis (IM) for the presence and distribution of EBV+ cells using EBER-specific in situ hybridization, in some cases combined with immunohistologic demonstration of cell type-characteristic antigens. In IM, large numbers of EBV+ lymphoid B blasts were detectable in extrafollicular areas, whereas germinal centers were generally free of EBV+ cells. In reactive lymph nodes, the frequency of EBV+ cells varied with the degree of lymphoid hyperplasia and underlying immune status. The lowest numbers of EBV+ cells were detected in nonactivated lymph nodes and highest in human immunodeficiency virus-associated lymphadenopathy. If present in these lymph nodes, EBV+ cells were almost exclusively localized to extrafollicular areas, as also observed in IM. However, in contrast to IM, these cells were mainly small lymphocytes. Furthermore, in some instances, occasional scattered EBV+ cells were seen within germinal centers, and in two cases diffuse expansions of EBV+ cells occurred within a single germinal center each, indicating that under certain circumstances EBV+ B lymphocytes may participate in physiologic germinal center reactions. These findings reflect the interference of EBV with physiologic lymphoid differentiation pathways and provide a link to EBV-associated malignant lymphomas with a postulated origin from germinal center cells.

B-Lymphocytes↗
PubMed1992

Immunohistochemical demonstration of the Epstein-Barr virus-encoded latent membrane protein in paraffin sections of Hodgkin's disease.

Paraffin sections from 46 cases of Hodgkin's disease were examined for the presence of the Epstein-Barr virus (EBV)-encoded latent membrane protein (LMP) using a sensitive (double layer alkaline phosphatase-anti-alkaline phosphatase) immunohistochemical method. LMP was detected in 22 cases, the majority of positive cases being of nodular sclerosis (12/24), mixed cellularity (6/7), and lymphocyte depletion (3/3) subtypes. Only one of 12 cases of lymphocyte predominant disease was positive. In all cases, reactivity was confined to Hodgkin's and Reed-Sternberg cells. These results provide further evidence for an association between EBV and Hodgkin's disease and indicate that LMP may be readily detected in archival material.

Herpesvirus 4, Human↗
PubMed1992

Epstein-Barr virus (EBV) and Hodgkin's disease in children: incidence of EBV latent membrane protein in malignant cells.

Previous studies have detected EBV DNA by Southern blotting or in situ hybridization in biopsy material from up to 30 per cent of adult cases of Hodgkin's disease. Here we have used monoclonal antibodies specific for the EBV latent membrane protein LMP1 to examine archival material from children with Hodgkin's disease. Material from 74 cases (54 males and 20 females) was examined and 37 (30 males and 7 females) were classified as LMP1-positive in the malignant cells. LMP1 positivity was present in 4/13 (31 per cent) of lymphocyte predominant, 14/36 (39 per cent) of nodular sclerosis, 17/20 (85 per cent) of mixed cellularity, 1/2 (50 per cent) of lymphocyte depletion, and 1/3 (33 per cent) of unclassified subtypes. The positive cases by clinical stage were I 9/22 (41 per cent), II 9/20 (45 per cent), III 11/24 (46 per cent), and IV 8/8 (100 per cent). LMP1 positivity was present in 2/5 (40 per cent) children aged less than 5 years, 12/27 (44 per cent) aged 5-10 years, and 23/42 (48 per cent) aged between 10 and 15 years. The association between EBV and Hodgkin's disease in children thus appeared to be more frequent in patients with mixed cellularity and advanced disease, but examples of EBV-positive tumours were found in all histological subtypes, stages, and ages. Stepwise discriminant function analysis showed that clinical stage IV and mixed cellularity histology are independently associated with LMP1 positivity. These observations indicate that Hodgkin's disease in children is at least as strongly linked to EBV as is the disease in adults.

Adolescent↗
PubMed1992

AgNOR counts and determination of malignancy in stromal tumours of the stomach and small intestine.

Twenty four primary stromal tumours of the stomach and small intestine were investigated by silver staining of interphase nucleolar organiser regions (AgNORs) in an attempt to obtain an objective criterion for prediction of malignant tumour behaviour. Malignant tumours tended to have higher AgNOR counts than their benign counterparts, but this increase was small and there was some overlap between the two groups. There was a correlation between the mean AgNOR count and the mitotic count. There was no correlation between tumour size and these two measurements. This study suggests that in these stromal tumours the AgNOR count is not a useful independent predictor of malignant behaviour.

Adolescent↗
PubMed1992

Correlation between histologic diagnosis mean nucleolar organizer region count and prognosis in canine mammary tumors.

In this study, surgically excised mammary tumors from 98 bitches were graded histologically, and the grade was compared with the mean nucleolar organizer region (NOR) count in silver-stained paraffin-embedded sections. Histologically benign tumors, papillary adenocarcinomas, and intraductal carcinomas showed relatively little variation; the mean count for each category was between three and four NOR per nucleus. There was, however, a significant increase in the NOR counts in tubular and solid carcinomas. This increase was most pronounced for tumors that showed evidence of infiltration into the surrounding connective tissues. The mean NOR count for noninfiltrative carcinomas was 5.1, and that for invasive carcinomas was 7.3 (P less than 0.03). The mean NOR count for individual carcinomas ranged from 2.0 to 12.3, and a significant correlation was found between an increased NOR count and tumor-related death during the first post-surgical year. The 39 bitches in which the tumor had an NOR count less than 8.0 had a generally favorable prognosis; only six (15%) died as a result of the original neoplasm. In contrast, 18/21 dogs (85%) with a carcinoma having an NOR count greater than 8.0 died from the tumor during the first post-surgical year. A similar, although less pronounced result was obtained specifically for invasive carcinomas, in which 3/12 (25%) tumors with an NOR count less than 6.0 resulted in the death of the host, compared with 17/20 (85%) that had an NOR count greater than 6. By using this technique, it is possible to identify a subgroup of bitches with invasive mammary carcinomas that have a very poor prognosis following apparently adequate surgical ablation of the primary tumor.

Animals↗