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Biomedical subjects

E W Kay

Publications and source records attributed to E W Kay.

At least 19 recordsLinked to original sources
PubMed1998

Altered expression of the p53-regulated proteins, p21Waf1/Cip1, MDM2, and Bax in ultraviolet-irradiated human skin.

The distribution of p21WAf1/CiP1, MDM2, and Bax/Bcl-2 proteins in ultraviolet (UV)-irradiated and nonirradiated human skin was examined immunohistochemically and compared with p53 protein levels. Sun-protected buttock skin from three volunteers was exposed to solar simulated irradiation, and biopsies were performed 0.5, 1, 2, 4, and 24 hours after irradiation as well as control unirradiated skin from the opposite buttock. A similar staining pattern was observed in each of the three volunteers. P53 protein was detectable in all skin samples examined. P21Waf1/CiP1 protein was visible in the nuclei of cells at 4 hours, and staining intensity increased at 24 hours. MDM2 protein expression was noted in isolated nuclei in the epidermis at 24 hours. Bax cytoplasmic staining was evident in the basal layer of the epidermis of all samples, and this staining appeared to increase in intensity in the 4- and 24-hour specimens. There was no Bcl-2 immunohistochemical staining in any sample. These results suggest that p53 and genes/proteins under the control of p53 are altered/ activated in normal human skin in response to UV exposure.

Aged↗
PubMed1998

Identification of vertical growth phase in malignant melanoma. A study of interobserver agreement.

Ninety-four H & E-stained slides of malignant melanoma were circulated to 6 pathologists in 2 university departments. For each slide, the growth phase of the lesion, Breslow thickness, and Clark level were determined by each observer. The aims of the study were to evaluate agreement between nonspecialist pathologists in identifying the vertical growth phase in malignant melanoma and to compare agreement for the growth phase with agreement for Breslow thickness and the Clark level. Our results show that although overall agreement for the growth phase is moderate, agreement between experienced observers is good. In fact agreement for the growth phase among this group was equal to the agreement for Breslow thickness. Overall agreement for Breslow thickness also was good but for the Clark level was only fair. These findings suggest that if the predictive value of the vertical growth phase proves to be robust, it will be used with an acceptable level of accuracy in routine diagnostic practice.

Humans↗
PubMed1998

Autoimmune chronic active hepatitis associated with the presence of antiphospholipid antibodies.

We report a patient with clinical, biochemical and immunological indices suggestive of autoimmune hepatitis with marked transaminasaemia, raised immunoglobulins and positive anti-nuclear and anti-smooth muscle antibodies. A coagulation screen revealed a transient, markedly increased, activated, partial thromboplastin time and a normal prothrombin time, with elevated levels of anticardiolipin antibodies and the presence of lupus anticoagulant, indicating the presence of antiphospholipid antibodies. Subsequent histology confirmed moderate hepatitis with piecemeal necrosis and fibrosis. Appropriate autoimmune therapy was commenced. This presentation illustrates the rare association of anti-phospholipid antibodies with autoimmune chronic active hepatitis presenting with a temporarily abnormal coagulation screen.

Actins↗
PubMed1998

Low-dose retinoid therapy for chemoprophylaxis of skin cancer in renal transplant recipients.

BACKGROUND: Renal transplant recipients have an increased incidence of skin cancers, which may be multiple and aggressive. OBJECTIVES: The purpose of this study was to examine the chemoprophylactic effects of low-dose etretinate (0.3 mg/kg/day) on skin cancer development in renal transplant recipients and to monitor retinoid toxic effects at this dose. METHODS: All skin lesions were counted and photographed prior to therapy with etretinate. Patients were assessed at monthly intervals for new skin lesions and for retinoid toxicity. RESULTS: Eleven renal transplant recipients participated. There was a significant reduction in the number of skin cancers which occurred during etretinate therapy compared with pre-treatment for 3 and 6 months of treatment, and a trend towards fewer skin cancers in the 12 and 18 month treatment periods. Side-effects were well-tolerated and no significant biochemical effects were observed. CONCLUSION: Low dose etretinate is safe, well-tolerated and partially effective in chemoprophylaxis of skin cancer in renal transplant recipients.

Adult↗
PubMed1998

Langerhans cells in benign, premalignant and malignant skin lesions of renal transplant recipients and the effect of retinoid therapy.

BACKGROUND AND DESIGN: Langerhans cells (LC) are a unique population of antigen-presenting cells in the epidermis which may play a role in the defense mechanisms against skin tumors. Renal transplant recipients (RTRs) have a significantly increased incidence of premalignant and malignant skin lesions. Langerhans cells, which are important for local immune surveillance, may be depleted or downregulated in skin neoplasms of RTRs, facilitating their growth. We investigated the Langerhans cell densities in 29 squamous cell carcinomas (SCCs), five basal cell carcinomas (BCCs), four Bowen's disease, eight dysplastic lesions (actinic keratoses), and three viral warts from 15 RTRs and compared these to the Langerhans cell densities in normal control skin. Eleven RTRs were receiving low-dose etretinate as chemoprophylaxis for recurrent skin cancer and the effect of low-dose retinoid therapy on Langerhans cell densities in SCCs from these patients was also assessed. Langerhans cells in frozen tissue sections were stained with the anti-human Leu-6 monoclonal antibody. RESULTS: There was no significant difference in LC numbers between normal skin from RTRs and normal skin from non-immunosuppressed individuals. There was a statistically significant reduction in LC/mm2 and LC/1000 K (keratinocytes) for SCC, BCC, dysplastic lesions and viral warts compared with normal skin (P < 0.001, P < 0.01, P < 0.001, P < 0.05, respectively). There was a trend for an increase in Langerhans cell density in SCCs which developed during etretinate therapy compared with pre-etretinate but the difference was not statistically significant. CONCLUSIONS: In this study of RTRs, a significant reduction in Langerhans cell densities was observed in SCCs, BCCs and dysplastic lesions compared with normal skin. A reduction in Langerhans cell density in viral warts from RTRs was also observed. A working hypothesis may include a multifactorial etiology for this reduction in Langerhans cell densities. It is possible that human papilloma virus (HPV) infection, by reducing intraepidermal Langerhans cell density, may decrease local immune surveillance and facilitate the development of skin cancers. Ultraviolet radiation and immune suppression may also play a role. The marked depletion of Langerhans cells in skin cancers, precursor lesions and viral warts suggests a central role for Langerhans cells in skin cancer promotion in RTRs.

Basal Cell Carcinoma↗
PubMed1997

p53 tumor suppressor gene protein expression in premalignant and malignant skin lesions of kidney transplant recipients.

BACKGROUND: Kidney transplant recipients have an increased incidence of skin cancer, the cause of which is likely multifactorial. Inactivation of the tumor suppressor gene p53 protein may be important. Chemoprophylaxis of skin cancer with retinoids is beneficial in these patients. OBJECTIVE: Our purpose was to investigate the immunohistochemical expression of p53 protein in premalignant and malignant cutaneous lesions in kidney transplant recipients and the effect of low-dose etretinate on p53 expression. METHODS: Paraffin sections were stained with the monoclonal antibody DO-7. RESULTS: Immunoreactivity of p53 was observed in 59% of basal cell carcinomas and more than 60% of squamous cell carcinomas, Bowen's disease, dysplastic lesions, and viral warts. No demonstrable effect of etretinate on p53 expression could be determined. CONCLUSION: The high prevalence of p53 immunoreactivity in premalignant and malignant skin lesions of kidney transplant recipients supports a role for p53 protein in skin cancer. This could be caused by mutation of the p53 gene, inactivation, or failure of degradation of p53 protein.

Adult↗
PubMed1997

Ploidy profile of morphologically normal squamous epithelium adjacent to high grade cervical intraepithelial neoplasia.

We have investigated the ploidy profile of morphologically normal mucosa adjacent to high grade CIN (n = 16) and also from normal cervix (n = 18). DNA ploidy was assessed using flow cytometry and image analysis. All cases were diploid by both modalities. Our results show that morphologically normal squamous mucosa has a stable ploidy profile even when it lies adjacent to high grade CIN. This finding supports the view that high grade CIN is a neoplastic expansion of transformed cells rather than the result of a field change effect.

Epithelium↗
PubMed1997

Mild abnormalities in liver histology associated with chronic hepatitis: distinction from normal liver histology.

BACKGROUND: Chronic hepatitis C virus infection associated with contaminated anti-D immunoglobulin has become an issue of recent concern. The clinical course of chronic hepatitis C infection is unpredictable and histological assessment is felt to be the most reliable means of assessing disease status. Semiquantitative scoring systems have been devised, which assess degree of necroinflammatory disease activity (grade) and extent of disease progression with fibrosis (stage) in chronic hepatitis. Often, using these systems, biopsies of anti-D associated chronic hepatitis C cases show mild changes only, with low scores. The significance of these low scores is uncertain. AIMS: To evaluate the significance of low scores in chronic hepatitis. METHODS: Liver biopsies were assessed from two groups of patients in whom liver histology would be expected to be normal: 30 cases of Gilbert's syndrome and 13 necropsy cases of young people (< 45 years) with no history or risk factors for liver disease. These biopsies were scored using the histological activity index of Knodell et al and its recent modification (separation of scores for grade and stage) by Ishak et al. RESULTS: Twenty of 30 cases of Gilbert's syndrome and 11 of the 13 necropsy cases had chronic hepatitis scores of 1 or 2, whereas only eight cases of Gilbert's and two necropsy cases had scores of 0. The remaining two Gilbert's cases had scores of 3 and 5. Similar results were found using both the histological activity index of Knodell et al and the method of Ishak et al. CONCLUSION: The finding of low but positive scores using these systems in people with normal liver histology questions the reliability and significance of finding such scores in patients with chronic hepatitis and is of particular concern in the evaluation of chronic hepatitis C infection.

Adult↗
PubMed1997

Screening of patients with iron overload to identify hemochromatosis and porphyria cutanea tarda.

OBJECTIVE: To assess the importance of iron overload as a risk factor for porphyria cutanea tarda (PCT). DESIGN: Prospective study during a 4-month period. SETTING: Departments of emergency care, gastroenterology, and dermatology in a tertiary referral center. PATIENTS: Patients were deemed eligible for inclusion in the study if serum ferritin levels were greater than 500 micrograms/L (normal range: females, < 125 micrograms/L; males, < 325 micrograms/L). MAIN OUTCOME MEASURES: Porphyrin excretion profiles were analyzed on all patients included in the study, where clinically relevant. A diagnosis of PCT was confirmed biochemically in all cases. The HLA typing was then performed on newly diagnosed cases of PCT. RESULTS: Of 4127 patients tested, 240 patients with an elevated serum ferritin level were identified, of whom 74 had an elevated serum ferritin level of more than 500 micrograms/L. Of the latter group, 17.5% had hemochromatosis and 6.7% had PCT. The incidence of PCT in the hemochromatosis group was 23%; HLA typing revealed the presence of at least 1 of the hemochromatosis markers. CONCLUSIONS: A high serum ferritin level in the absence of evident cause should prompt investigation for both hemochromatosis and PCT. The HLA heterozygosity for hemochromatosis in some patients with PCT may be a cause of hepatic siderosis.

Adult↗
PubMed1996

An image analysis study of DNA content in early colorectal cancer.

The DNA content of 168 consecutive T3,N0,M0 (Dukes' B, Astler-Coller B2) colorectal cancers was studied using image analysis on formalin-fixed paraffin-embedded tissues. 72 cases (43%) were classified as diploid and the remaining 96 (57%) as non-diploid. After a median follow-up period of 6.7 years, a significant survival advantage was found for diploid compared with non-diploid cases (logrank test; P = 0.008). The long-term (8 year) survival rate was 70% for diploid and 46% for non-diploid tumours. Subgroup analysis showed that the survival advantage conferred by tumour diploidy was greatest in large (> or = 5 cm) cancers and was found both in colonic and rectal cancer cases. These data indicate that tumour ploidy status measured by image analysis might be useful in determining risk of colorectal cancer recurrence and death in patients following resection of early colorectal cancer.

Adult↗
PubMed1996

Porphyrin metabolism in hepatitis C infection.

Hepatitis C virus has been implicated as a major precipitating factor in porphyria cutanea tarda (PCT). To determine whether hepatitis C infection alone is sufficient to induce PCT, we screened two groups of patients with hepatitis C infection. The first group comprised women who had become HCV positive secondary to immunization with anti-D immunoglobulin (group 1). Group 2 included males and females who were HCV positive but HIV negative secondary to intravenous drug abuse. Though both groups had very abnormal liver function tests, we found no significant abnormalities in porphyrin metabolism in these groups of patients. Therefore, in this study population, we conclude that HCV infection alone is insufficient to cause porphyrin metabolic derangement.

Adolescent↗
PubMed1996

Proliferation indexes--a comparison between cutaneous basal and squamous cell carcinomas.

AIMS: To compare differences in cell proliferation indexes and apoptotic indexes between cutaneous basal and squamous cell carcinomas, in an attempt to suggest an explanation for the differences in their biological behaviour. METHODS: Forty cases of cutaneous basal cell carcinoma (BCC) and 40 cases of moderately and well differentiated squamous cell carcinoma (SCC) were retrieved from the archives. Sections, 4 microns thick, were cut from formalin fixed, paraffin wax embedded tissue in each case and stained with haematoxylin and eosin. These were then examined for mitotic and apoptotic figures per 1000 cells. Sections from the same cases were also immunostained with the mouse monoclonal antibody Ki67 (MIB1); positive nuclear staining was counted per 1000 cells. RESULTS: No significant differences were found between the mitotic indexes and apoptotic indexes in these tumours. There was, however, a significant difference in Ki67 (MIB1) staining, with greater staining in the squamous cell carcinomas. CONCLUSION: Estimation of the mitotic and apoptotic indexes did not reveal any differences between these two tumour types. The proliferation indexes, assessed by Ki67 immunostaining, did differ. This may be one of the factors underlying the more aggressive behaviour of SCC.

Apoptosis↗
PubMed1996

Inter-observer variation of p53 immunohistochemistry--an assessment of a practical problem and comparison with other studies.

The aims of this study were to analyse the expression of p53 by immunohistochemistry in a range of malignant and pre-malignant conditions and to assess the degree of inter-observer variability in interpretation of p53 immunostaining. Formalin-fixed paraffin-embedded sections from 28 colorectal carcinomas (CRC), 40 cervical intraepithelial neoplasia lesions (CIN), 22 transitional cell carcinomas of the bladder (TCC), 10 invasive squamous carcinomas of uterine cervix and 21 squamous cell carcinomas of skin were examined. A polyclonal antibody was used in 90 cases. A monoclonal antibody was used in the remainder. Ten cases were stained with both. Aberrant expression of p53 protein was documented in 48% of squamous cell carcinomas of skin, 29% of CRC, 22% of CIN and 23% of TCC. All cases of squamous cell carcinoma of uterine cervix were negative. Inter-observer variation occurred in 7% of cases examined. This was confined to two tumour groups, TCC and CIN. Our results showed that p53 oncoprotein expression by immunohistochemistry was identified in 26% of cases but the range was wide (0-48%) and appeared to be tumour specific. Inter-observer variability in the interpretation of immunohistochemical staining was low (7%) and was restricted to two tumour groups.

Biomarkers, Tumor↗
PubMed1996

Evaluation of p53 protein expression in renal cell carcinoma: comparison of two antibodies.

The aims of this study were to establish a profile for the expression of p53 in primary renal cell carcinoma using the polyclonal antibody NCL-CB1 and the monoclonal antibody D07, and to compare the results of staining with both antibodies. Ninety-six cases were studied using formalin-fixed paraffin-embedded tissue. Positive nuclear staining ranged from 5% (D07) to 12% (NCL-CM1). Positive cytoplasmic staining ranged from 7% (D07) to 25% (NCL-CM1) of cases. Interobserver agreement was excellent. The findings suggest that such a low level of immunohistochemical positivity reduces any potential prognostic value for p53 in this tumour type.

Antibodies↗
PubMed1995

The pathology of cervical cancer.

The significant changes over the last decade in the CIN/cervical carcinoma area have involved the increasing recognition of many cervical carcinomas as adenocarcinomas, rather than squamous cell type, and their propensity for arising in young women. Another area of interest is the deployment of new molecular techniques that are unveiling the role of oncogene co-factors (e.g. HPV, p53) in the biologic evolution of CIN and hopefully glandular dysplasia.

Adenocarcinoma↗
PubMed1994

Soft tissue and visceral sarcomas in Irish patients. Interim analysis of data obtained by the Dublin Soft Tissue Tumour Panel.

The Dublin Soft Tissue Sarcoma Panel was established in 1989 with a view to achieving a unified approach to diagnosis and management of soft tissue and visceral sarcomas. This interim report presents data on 265 prospectively-evaluated patients and on a separate retrospective series of 126 patients. The patients in the prospective series were treated by 93 different surgical and medical specialists. Tumours presented in all anatomic sites and ranged in size from 0.2 to 60 cm. Leiomyosarcoma was the commonest tumour type. Eighty-nine tumours were inoperable at clinical presentation. There was a consensus panel diagnosis in over 90%, non-neoplastic reactive lesions and primitive round cell tumours being the most difficult cases diagnostically. Management, including onward referral for chemotherapy or radiation therapy, was inconsistent. The 2-year survival figures were: 43% (1989-91) and 37% (1980-88). These findings should provide a basis for the evaluation of coherent treatment strategies for Irish sarcoma patients.

Adolescent↗