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J Crocker

Publications and source records attributed to J Crocker.

At least 37 records · Page 2Linked to original sources
PubMed2001

Apoptosis in squamous cell carcinoma of the lung: correlation with survival and clinicopathological features.

AIMS: Apoptosis is recognised as a physiological mechanism for controlling cell numbers and its subversion is thought to contribute to carcinogenesis. The aims of this study were to measure the apoptotic index (AI) in a series of squamous cell carcinomas (SCCs) of the lung using standard histological staining and confirm this by immunohistology using an antibody to an apoptosis specific protein (ASP), and to seek to correlate the AI with clinicopathological parameters. METHODS: Sections of 134 SCCs were stained by haematoxylin and eosin (H&E) for counting apoptotic bodies of determine the AI (number of apoptotic bodies/10,000 tumour cells); 26 of these were also stained with anti-ASP antibody and the proportion of ASP positive cells counted. Clinical data were obtained from hospital notes. RESULTS: The mean AI obtained by H&E staining of all 134 SCCs was 30.3 (SD, 24.75). Anti-ASP staining allowed easy identification of apoptotic bodies, and generated a somewhat higher index (mean, 51.4; SD 39); this was not a result of the selection of tumours because the AI by H&E in the subset stained with anti-ASP was 31.1. Regression analysis showed that the correlation between the two values of AI was highly significant (Rs = 0.9760; p < 0.001), indicating that the two methods were both reliable measures of apoptosis but that the anti-ASP staining is the more sensitive method. The tumours were grouped into high AI (> 50) and low AI (< 50) and survival analysis was carried out. The mean survival of the high AI group was 109 weeks and of the low AI group 72 weeks (p = 0.036). CONCLUSIONS: Anti-ASP staining is a reliable, easy, and sensitive method for assessing apoptosis in tumour sections and confirms the validity of the AI obtained by H&E staining. AI is a guide to the behaviour of SCCs of the lung.

Adult↗
PubMed2000

Apoptosis of malignant cells in Hodgkin's disease is related to expression of the cdk inhibitor p27KIP1.

Previous results from B-cell chronic lymphocytic leukaemia suggest that expression of p27KIP1 might be important in protection from apoptosis. Given the relevance of apoptosis to the pathogenesis of Hodgkin's disease (HD), it was decided to examine the expression of p27KIP1 in relation to apoptosis in these lesions. Paraffin-wax sections from a total of 65 histologically confirmed HD tumours were used to derive apoptotic index (AI) and DNA fragmentation index (DFI) scores, which were compared with the expression of various cell-cycle-regulating proteins, including p27KIP1 (p27), p21WAF1/CIP1 (p21) and cyclin D1, and with Epstein-Barr virus (EBV) status. The DFI was measured by TdT-mediated dUTP-FITC nick end-labelling (TUNEL), and the AI by conventional morphology. Cells showing the typical morphology of apoptosis, together with those resembling so-called 'mummified' Hodgkin/Reed-Sternberg (HRS) cells, were included in AI measurements. Increasing numbers of p27-positive HRS cells were associated with lower levels of apoptosis in these cells, as indicated by significantly lower AI and DFI scores. There was a trend towards poorer survival in those patients with the highest numbers of p27-positive HRS cells and with lower AI and DFI scores, but these differences were not statistically significant. p21-positive HRS cells were significantly more frequent in those cases with lower AI scores. A similar trend was observed for p21 and DFI, although this relationship was not statistically significant. There was also a trend towards higher levels of cyclin D1 protein in HD cases with high AI and DFI values. A tendency for increasing numbers of p27-positive and p21-positive HRS cells in EBV-positive cases was noted, but this relationship was not statistically significant. EBV status did not correlate with either AI or DFI scores. The results of this study suggest that p27, and possibly also p21, may be involved in protection from apoptosis in HD.

Apoptosis↗
PubMed2000

Variation in the frequency of Epstein-Barr virus-associated Hodgkin's disease with age.

A number of studies in developed countries have reported variation in the frequency of Epstein-Barr virus (EBV)-associated Hodgkin's disease (HD) with age. A 'three disease' model for HD that incorporates the EBV association, histological subtype of HD and age has recently been proposed. In this model, Hodgkin's disease of childhood and older adults is commonly EBV-associated and of mixed cellularity type, whereas young adult HD is generally not EBV-associated and is usually characterised by nodular sclerosis disease. A case series of HD diagnosed in the West Midlands between 1981 and 1997, inclusive, was used to investigate the applicability of the 'three disease' model. In situ hybridisation for the EBV early RNAs (EBERs) was used to determine the presence of EBV in the malignant Hodgkin/Reed-Sternberg cells. In contrast to the 'three disease' model, nodular sclerosis was the predominant subtype in each of the age groups within the case series. In addition, overall there was little variation in EBV-positive rates across the age ranges examined. However, when females were analysed separately, older women (45+ years) were significantly more likely to have EBV-positive disease than their younger counterparts (<45 years). In summary our results do not generally support the 'three disease' model.

Adolescent↗
PubMed2000

Parent satisfaction with education, support, and decision-making regarding their children's central venous access devices.

This descriptive, exploratory study assessed parents' satisfaction with the education and support they received before and after their children had central venous access devices (CVADs) inserted for cancer treatment. Decisions regarding the type of CVAD and parent satisfaction with that choice were also evaluated. Parents of children who experienced a CVAD during the six-year period 1992-1997 participated. Data were collected through telephone interviews using a questionnaire specifically designed for the purposes of the study. Results suggest that parents were satisfied with the teaching and support received both prior to and following CVAD insertion. Other findings reveal that not all parents take part in decisions about the type of device used, and that if given a choice, based on their experience, they would likely choose implanted ports over Hickman catheters.

Adult↗
PubMed1999

Effect of Epstein-Barr virus infection on response to chemotherapy and survival in Hodgkin's disease.

We have analyzed paraffin sections from 190 patients with histologically confirmed Hodgkin's disease (HD) for the presence of Epstein-Barr virus (EBV) using in situ hybridization to detect the EBV-encoded Epstein-Barr virus early RNAs (EBERs) and immunohistochemistry to identify latent membrane protein-1 (LMP1) expression. EBV was present in the tumor cells in 51 HD cases (27%) and was mainly confined to the mixed cellularity and nodular sclerosis subtypes. There was no difference between EBV-positive and EBV-negative HD patients with regard to age, clinical stage, presentation, and the number of alternating chemotherapy cycles of ChIVPP and PABIOE received. The complete remission rate after study chemotherapy was 80% in EBV-positive patients versus 69% in EBV-negative patients (P =.05). The 2-year failure-free survival rate was significantly better for EBV-positive patients when compared with the EBV-negative HD group (P =.02). Although 2-year and 5-year overall survival rates were better for EBV-positive HD patients, the differences were not statistically significant (P =.18 and P =.40, respectively). In conclusion, the results confirm the favorable prognostic value of EBV in the tumor cells of HD patients and suggest important differences in response to chemotherapy between EBV-positive and EBV-negative patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

CD40 and Bcl2 expression in squamous cell carcinoma of the lung: correlation with apoptosis, survival, and other clinicopathological factors.

CD40 is a cell surface receptor which, when ligated, modulates apoptosis in some cell types, perhaps via activation of the expression of members of the Bcl2 gene family. This study sought to determine whether expression of CD40 in a series of 134 squamous cell carcinomas (SCCs) of the lung was related to apoptosis or clinical parameters, either alone or in connection with Bcl2 expression. Sections of SCCs were stained for CD40 and Bcl2 by immunohistochemical techniques. An index was determined for these two markers by counting stained and unstained malignant cells under high power. Sections were also stained by haematoxylin and eosin for determination of the apoptotic index by counting apoptotic bodies. About 40 per cent of SCCs expressed CD40 in at least some of the malignant cells, with about 10 per cent essentially uniformly stained. Similar proportions expressed Bcl2, with a tendency for expression to be mutually excluisve. Apoptosis did not correlate with CD40 expression, nor was there evidence of a co-operative or an antagonistic effect with Bcl2. Bcl2 expression, on the other hand, correlated significantly with the apoptosis score. CD40 expression showed no significant relationship with survival or any other clinicopathological parameter except ploidy. Bcl2 expression, however, correlated with longer survival. It is concluded that CD40 expression in SCC of the lung does not by itself relate to apoptosis, nor is it a useful indicator of prognosis.

Adult↗
PubMed1999

When ideology hurts: effects of belief in the protestant ethic and feeling overweight on the psychological well-being of women.

Two studies addressed the relationship between Protestant ethic (PE) ideology and psychological well-being for self-perceived overweight and normal weight women. In Study 1, PE beliefs interacted with self-perceived weight status: For very overweight women, higher PE beliefs were related to lower psychological well-being, whereas the opposite pattern emerged for normal weight women. The relationship of PE to well-being was not mediated by beliefs about controllability of weight or dislike of the overweight. In Study 2, either a PE ideology or an inclusive ideology was primed within the context of the stigma of overweight. For overweight participants, priming PE ideology led to decreased psychological well-being, whereas priming an inclusive ideology led to increased psychological well-being. Normal weight participants were unaffected. PE ideology as a vulnerability factor for the psychological well-being of the overweight is discussed.

Adolescent↗
PubMed1999

Effect of material deprivation on Epstein-Barr virus infection in Hodgkin's disease in the West Midlands.

We have used Townsend scores from postcode data to compare levels of material deprivation and Epstein-Barr virus (EBV)-positivity for 223 patients diagnosed with Hodgkin's disease (HD) in the period 1981-1997. The presence of EBV in HD tumours was determined using in situ hybridization to target the abundantly expressed EBV early RNAs. EBV was detected in the malignant Hodgkin and Reed-Sternberg cells in 47/223 HD cases (21%). There was found to be a tendency for higher Townsend scores (indicative of higher levels of material deprivation) in EBV-positive HD patients, but this association was not statistically significant. When various subgroups of patients from the study were examined separately the indication of higher Townsend scores in EBV-positive patients was found to be more marked for patients with mixed cellularity disease (P = 0.09) and for females (P = 0.03). The results of this study suggest that differences in the level of material deprivation are important in determining the likelihood of EBV-positive HD in the UK, particularly for certain subgroups of patients. It is not known what specific socioeconomic factors are responsible for these differences, although alterations in the timing or rate of primary EBV infection, or decline in the level of EBV-specific immunity, may be important.

Adolescent↗
PubMed1998

Analysis of major histocompatibility complex class I, TAP expression, and LMP2 epitope sequence in Epstein-Barr virus-positive Hodgkin's disease.

The Epstein-Barr virus (EBV)-encoded latent membrane proteins, LMP1 and LMP2, are consistently expressed by the malignant Hodgkin/Reed-Sternberg (HRS) cells of EBV-associated Hodgkin's disease (HD). Cytotoxic T lymphocyte (CTL) responses to both of these proteins have been shown in the blood of EBV-seropositive individuals, yet in HD the apparent failure of the CTL response to eliminate HRS cells expressing LMP1 and LMP2 in vivo has given rise to the suggestion that HD may be characterized by the presence of defects in antigen processing/presentation or in CTL function. This study has used immunohistochemistry to show high-level expression of major histocompatibility complex (MHC) class I molecules by the HRS cells of EBV-associated HD and either low level or absence of expression of MHC class I molecules on HRS cells of EBV-negative tumors. In addition, HRS cells expressed high levels of transporter-associated proteins (TAP-1, -2), irrespective of the presence of latent EBV infection. These results suggest that global downregulation of MHC class I molecules does not account for the apparent ability of EBV-infected HRS cells to evade CTL responses, but may be important in the understanding of EBV-negative disease. We have also sequenced an epitope in LMP2A (CLGGLLTMV) that is restricted through HLA A2.1, a relatively common allele in Caucasian populations, and showed that this epitope is wild type in a small group of EBV-associated HLA A2.1-positive HD tumors. This result may be relevant to proposed immunotherapeutic approaches for EBV-positive HD patients that target CTL epitopes.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Antigen presenting phenotype of Hodgkin Reed-Sternberg cells: analysis of the HLA class I processing pathway and the effects of interleukin-10 on epstein-barr virus-specific cytotoxic T-cell recognition.

Approximately 40% of Hodgkin's disease (HD) cases in Western countries carry Epstein-Barr virus (EBV) in the malignant Hodgkin-Reed-Sternberg (H-RS) cells. HLA class I-restricted cytotoxic T lymphocytes (CTLs) with specificity for viral antigens expressed in H-RS cells therefore have therapeutic potential. However, a prerequisite for CTL therapy is that the tumor target be capable of processing and presenting endogenously expressed antigens via the transporter associated with antigen processing (TAP)-dependent HLA class I pathway. We have assessed the antigen-presenting phenotype of H-RS cells in two ways. First, immunohistochemical analysis of 38 HD biopsies showed that H-RS cells were uniformly TAP1/TAP2-positive and expressed HLA class I in the majority (18 of 24, 75%) of EBV-positive cases compared with only 4 of 14 (29%) of EBV-negative cases. Second, using a panel of 5 H-RS cell lines, we showed that 4 of 5 could process and present EBV proteins to HLA class I-restricted EBV-specific CTL clones. Others have reported that human interleukin-10 (IL-10), which is expressed by H-RS cells in the majority of EBV-positive HD cases, can abrogate CTL recognition in some circumstances. However, IL-10 pretreatment of the H-RS lines or of the EBV-specific CTLs had no such effect in this system. These results support the possibility that EBV-specific CTLs may be used to treat virus-positive HD.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Familial pancreatic lymphoma.

Non-Hodgkin's lymphoma is not commonly a familial condition. This is believed to be the first two cases of primary pancreatic lymphoma within a single family. The two cases, a brother and sister, both presented in their 60s and were diagnosed histologically as having high grade B cell lymphoma affecting the pancreas, an uncommon primary site. Both responded well to treatment with chemotherapy and were in remission at the time of writing. On further investigation it was found that their mother also presented with a malignant lymphoma of cervical nodes 30 years earlier and subsequently died of the disease.

Aged↗
PubMed1997

Distinction between pleural mesothelioma and pulmonary adenocarcinoma using MOC31 in an asbestos sprayer.

Asbestos exposure may cause asbestosis, pleural plaques and benign pleural disease, and may pre-dispose to malignant mesothelioma and other neoplasms. The occurrence to two primary tumours in the same patient is rare, and the appearance of a pleural mesothelioma and another lung tumour is exceptional. The present case report describes a patient who, by standard immunohistochemistry, was thought to have mesothelioma at pleuro-pneumonectomy, and adenocarcinoma in the other lung at post-mortem 5 months later. Subsequent investigation using the MOC31 antibody demonstrated a single pathology of adenocarcinoma of the lung. The additional use of this antibody has important histopathological and legal implications.

Adenocarcinoma↗
PubMed1997

The evaluation of salivary gland tumours using proliferating cell nuclear antigen.

In order to assess its discriminating and prognostic value, we studied the immunoreactivity for proliferating cell nuclear antigen (PCNA) in tissue from 52 human salivary gland tumours using the murine monoclonal antibody PC10. The PCNA percentage count, namely, the average number of positive nuclei counted per 100 randomly selected tumour cells was recorded for each tumour. Anaplastic carcinoma was used as a positive control and histologically 'normal' salivary gland and tonsil served as a negative control. A PCNA count of 30 per cent was postulated to predict malignancy within a given salivary gland tumour i.e. a PCNA count of 30 per cent or above would indicate malignant potential. This gave a sensitivity of 96.9 per cent and a specificity of 95.2 per cent and a positive predictive value of determining malignancy of 96.8 per cent. We conclude that PCNA immunoreactivity is useful in discriminating between benign and malignant salivary gland tumours and that it may have prognostic value in this diverse group of neoplasms.

Biomarkers, Tumor↗