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Biomedical subjects

P Maxwell

Publications and source records attributed to P Maxwell.

At least 55 records · Page 3Linked to original sources
PubMed1999

Genetic, morphometric and immunohistochemical markers of latent coeliac disease.

BACKGROUND: It is recognized that coeliac disease may exist in a latent form characterized by HLA-DR3 and increased counts of intra-epithelial lymphocytes (IELs) and gamma/delta T cells in jejunal biopsies. To determine whether subjects with persistent serological markers 4 and 13 years after a population screening survey have the HLA constitution of coeliac disease and/or minor morphometric abnormalities of the small intestine, including raised gamma/delta T-cell counts, as possible indicators of latent coeliac disease. SUBJECTS: Participants with positive serology detected by the Belfast MONICA Project surveys (1983 and 1991) were subdivided into those with persistently positive serology (persistent serology), negative serology at follow-up (transient serology) and those with enteropathy (coeliac disease). Morphometric features were compared with MONICA controls who had negative serology and HLA antigen frequencies were compared with blood donor controls. METHODS: Subjects were followed up in 1994-1996 and were re-tested for IgA antibodies to gliadin, endomysium and reticulin. HLA typing was carried out and IELs and gamma/delta T-cell counts were assessed in jejunal biopsies in subjects who gave consent. RESULTS: Persistent serology mainly concerned antigliadin (AGA) and antireticulin (ARA) antibodies but one patient had positive antiendomysial antibody (EMA) and ARA in 1983, which became negative at follow-up, at which time they were positive for AGA. No significant differences were observed between IELs or gamma/delta T-cell counts when the persistent and transient groups were compared in turn with the MONICA controls. HLA-DR2 was expressed in 11 of 16 in the persistent group compared to 47 of 150 blood donor controls (P = 0.013). HLA-DR3 occurred in 15 of 17 coeliac patients compared to 37 of 150 blood donors (P = 0.00001). CONCLUSIONS: Persistent serological markers following population screening do not appear to indicate latent coeliac disease.

Adult↗
PubMed1999

Cyclosporin associated gingival overgrowth in renal transplant recipients.

OBJECTIVES: To investigate the prevalence and severity of gingival overgrowth in a group of renal transplant recipients treated in one centre in Northern Ireland. STUDY DESIGN: A consecutive group of patients who had had a renal transplant for at least 6 months and were attending the Renal Unit in Belfast City Hospital took part in the study. These were divided into a group of 84 subjects treated with cyclosporin since their transplant who were compared with a control group of 36 transplant recipients who had never received cyclosporin. Each subject had a periodontal examination and completed a questionnaire. The severity of gingival overgrowth was scored from plaster models. OUTCOME MEASURES: Clinically significant gingival overgrowth was equated with a score of > or = 30 using the index developed by Seymour et al (1985). RESULTS: 41 (49%) of the cyclosporin group had clinically significant gingival overgrowth compared with none of the controls. A significantly higher proportion of males had overgrowth than females. There were significant correlations between age at transplant, plaque, bleeding, pocketing and the severity of gingival overgrowth. Many patients with clinically significant gingival overgrowth were apparently unconcerned about this condition. CONCLUSIONS: It is concluded that gingival overgrowth is a significant problem for renal transplant patients treated with cyclosporin, particularly if they are also treated with a calcium channel blocker. None of the factors measured, in isolation, explained the variable expression of gingival overgrowth in those at risk.

Adult↗
PubMed1999

Use of alcohol fixed cytospins protected by 10% polyethylene glycol in immunocytology external quality assurance.

AIMS: To provide cytospins as a means of external quality assurance (EQA), while maintaining antigen expression integrity and achieving uniformity of material for all participating laboratories. METHODS: Cells were collected from two adenocarcinoma and one reactive pleural effusion specimens. Lymphoid cells were also collected through aspiration of a resected tonsil specimen. All cells were collected in Hanks balanced salt solution (HBSS); cytospins were made and fixed in methanol or acetone alone or protected using a layer of 10% polyethylene glycol (PEG) in 50% methanol. Two laboratories participated (RGHT and UCL). RESULTS: Cytokeratin expression detected using either CAM5.2 or AE1/AE3 antibodies was sensitive to temperature. Without PEG, unacceptable or negative staining was seen within six weeks of preparation. LCA was not sensitive to temperature, with good staining scores being achieved after eight weeks following preparation. CONCLUSIONS: It is possible to send alcohol fixed, air dried cytospins to laboratories participating as part of an EQA scheme for immunocytology. Some antigens will require protection from temperature variations during transit. A layer of 10% PEG in 50% methanol, allowed to air dry, is suitable for this purpose. Participating laboratories will only have to remove this layer using methanol before their localisation technique for assessment.

Adenocarcinoma↗
PubMed1999

Fluorescence in situ hybridisation detection of erbB2 amplification in breast cancer fine needle aspirates.

AIM: To develop a method for the detection of amplification of the erbB2 oncogene in breast cancer fine needle aspirates using fluorescence in situ hybridisation (FISH) and to compare amplification with immunohistochemical detection of the erbB2 protein. METHODS: A digoxigenin labelled probe to the erbB2 gene was hybridised to 15 aspirates prepared from operative breast cancer specimens. A chromosome 17 centromere probe was also hybridised to the aspirates either separately or in combination with the erbB2 probe. The aspirates were scored for erbB2 amplification and chromosome 17 centromere number. Subsequently, paraffin wax embedded sections of the tumours were stained with the antibody CB11 and scored for the presence of membrane staining. RESULTS: Three of the 15 tumour aspirates showed high level amplification of erbB2 detected by FISH. These three tumours also showed chromosome 17 polysomy and diffuse membrane staining by immunohistochemistry. CONCLUSIONS: FISH can be used to detect erbB2 amplification in fine needle aspirates and results correlate with conventional immunohistochemical staining. Difficulties were encountered in the visualisation of the signals in non-amplified cases without the use of specialised digital imaging.

Biopsy, Needle↗
PubMed1999

Carcinoembryonic antigen: cell adhesion molecule and useful diagnostic marker.

Carcinoembryonic antigen (CEA) was first identified over 30 years ago as a marker of malignant colonic cells, but has since been shown to be expressed by a range of normal epithelial cells. Moreover, CEA is one member of a larger gene family and shares structural homology with other family molecules. Despite this confused picture, CEA is now known to function in several biological roles, including cell-cell adhesion. Its use in the diagnostic setting has also changed over the years, where in routine immunohistochemistry, monoclonal antibodies to CEA are useful in aiding diagnosis when used as part of a panel. Here, recent advances in understanding the biological role(s) that CEA and CEA-related antigens may play in cell adhesion are highlighted, together with results from molecular studies that illustrate how structure can influence the choice of CEA antibodies for use in both the research and diagnostic laboratory.

Biomarkers, Tumor↗
PubMed1998

Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis.

As a result of deprivation of oxygen (hypoxia) and nutrients, the growth and viability of cells is reduced. Hypoxia-inducible factor (HIF)-1alpha helps to restore oxygen homeostasis by inducing glycolysis, erythropoiesis and angiogenesis. Here we show that hypoxia and hypoglycaemia reduce proliferation and increase apoptosis in wild-type (HIF-1alpha+/+) embryonic stem (ES) cells, but not in ES cells with inactivated HIF-1alpha genes (HIF-1alpha-/-); however, a deficiency of HIF-1alpha does not affect apoptosis induced by cytokines. We find that hypoxia/hypoglycaemia-regulated genes involved in controlling the cell cycle are either HIF-1alpha-dependent (those encoding the proteins p53, p21, Bcl-2) or HIF-1alpha-independent (p27, GADD153), suggesting that there are at least two different adaptive responses to being deprived of oxygen and nutrients. Loss of HIF-1alpha reduces hypoxia-induced expression of vascular endothelial growth factor, prevents formation of large vessels in ES-derived tumours, and impairs vascular function, resulting in hypoxic microenvironments within the tumour mass. However, growth of HIF-1alpha tumours was not retarded but was accelerated, owing to decreased hypoxia-induced apoptosis and increased stress-induced proliferation. As hypoxic stress contributes to many (patho)biological disorders, this new role for HIF-1alpha in hypoxic control of cell growth and death may be of general pathophysiological importance.

Animals↗
PubMed1998

Comparison of p53 and DNA content abnormalities in adenocarcinoma of the oesophagus and gastric cardia.

This study examined the association between 17p allelic loss, p53 gene mutation, p53 protein expression and DNA aneuploidy in a series of adenocarcinomas arising in the oesophagus and gastric cardia. 17p allelic loss was detected in 79% (15 of 19) of oesophageal and in 83% (29 of 35) of gastric adenocarcinomas. p53 mutations were detected in 70% (14 of 20) and 63% (26 of 41) of oesophageal and of gastric adenocarcinomas respectively. Both tumour types were associated with a predominance of base transitions at CpG dinucleotides. In five cases of oesophageal adenocarcinoma, the same mutation was detected both in tumour and in adjacent dysplastic Barrett's epithelium. Diffuse p53 protein expression was detected in 65% (13 of 20) and 59% (24 of 41) of oesophageal and of gastric tumours, respectively, and was associated with the presence of p53 missense mutation (Chi-squared, P < 0.0001). DNA aneuploidy was detected in 80% (16 of 20) of oesophageal and in 70% (28 of 40) of gastric tumours. No association was found between p53 or DNA content abnormalities and tumour stage or histological subtype. In conclusion, this study detected a similar pattern of p53 alterations in adenocarcinoma of the oesophagus and gastric cardia--molecular data consistent with the observation that these tumours demonstrate similar clinical and epidemiological features.

Adenocarcinoma↗
PubMed1998

Localization of the cellular expression of inhibin in trophoblastic tissue.

AIMS: Inhibin is a peptide hormone which is normally produced by ovarian granulosa cells and which inhibits the release of follicle stimulating hormone from the pituitary gland, thus acting as a modulator of folliculogenesis. Serum inhibin levels are higher during pregnancy than during the normal menstrual cycle and the placenta is thought to be a source of circulating inhibin. Previous studies have yielded conflicting results as to the cellular localization of inhibin in the placenta and the aim of the present study was to investigate the immunohistochemical localization of the hormone in placental tissue. We also wished to investigate whether inhibin could be demonstrated in choriocarcinoma and in non-gestational trophoblastic tissue. MATERIALS AND RESULTS: Immunohistochemical staining was performed using a monoclonal antibody against the alpha subunit of human inhibin. Specimens included in the study were intrauterine products of conception (n = 36), extrauterine products of conception (n = 4), decidualized endometrium (n = 15), extrauterine decidualized tissue (n = 3), hydatidiform mole (n = 5), uterine choriocarinoma (n = 2) and testicular embryonal carcinoma with syncytiotrophoblast giant cells (n = 6). In cases of products of conception, including hydatidiform mole, there was consistent strong positive staining of syncytiotrophoblast but no staining of cytotrophoblast with anti-inhibin. Staining with anti-inhibin highlighted trophoblastic cells within the placental bed. In a small number of cases there was focal weak positive staining of decidua. There was positive staining of the two cases of uterine choriocarcinoma and of syncytiotrophoblast giant cells in the six cases of testicular embryonal carcinoma. CONCLUSIONS: The study shows that immunohistochemically detectable inhibin alpha subunit in placental tissue is mainly localized within syncytiotrophoblast although in some cases there is also positive staining of decidua. Production of inhibin by these cells may account for raised serum levels during pregnancy. Inhibin can also be demonstrated in choriocarcinoma and in nongestational trophoblastic tissue. Inhibin is a sensitive marker of syncytiotrophoblast and staining with this antibody may prove useful in the diagnosis of choriocarcinoma and in the demonstration of trophoblastic cells in germ cell tumours.

Carcinoma, Embryonal↗
PubMed1998

Immunohistochemical study of testicular sex cord-stromal tumors, including staining with anti-inhibin antibody.

Inhibin is a peptide hormone produced by ovarian granulosa cells and testicular Sertoli cells. Ovarian granulosa cell and other sex cord-stromal tumors usually exhibit positive immunohistochemical staining with antiinhibin antibodies, and this may be valuable in differentiating these neoplasms from histologic mimics. In the present study, we investigated the immunohistochemical staining of testicular sex cord-stromal tumors using antiinhibin. Immunostaining with CAM5.2, vimentin, S-100 protein, desmin, epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), and placental alkaline phosphatase (PLAP) also was performed because few studies have investigated in detail the immunophenotype of testicular sex cord-stromal tumors. Fifteen of 16 Leydig cell tumors exhibited strong positive staining with antiinhibin. A proportion of Leydig cell tumors also stained positively with CAM5.2 (7 of 16), vimentin (14 of 16), S-100 protein (10 of 16), desmin (2 of 16) and epithelial membrane antigen (4 of 16). Four of six testicular sex cord-stromal tumors with varying degrees of Sertoli or granulosa cell differentiation were positive with antiinhibin, as were two of three sex cord-stromal tumors that were unclassified. Some of these tumors were positive with CAM 5.2, vimentin, S-100 protein, desmin, and epithelial membrane antigen. All tumors were negative with carcinoembryonic antigen and placental alkaline phosphatase. The immunohistochemical findings show that, analogous to their ovarian counterparts, most testicular sex cord-stromal tumors are immunoreactive with antiinhibin. Immunohistochemistry using this antibody as part of a panel may be valuable in confirming a diagnosis of testicular sex cord-stromal tumor and in differentiating these neoplasms from others that may mimic them.

Antibodies, Monoclonal↗
PubMed1998

Immunohistochemical detection of metallothionein and MIB1 in uterine cervical squamous lesions.

Metallothioneins (MTs) are ubiquitous low molecular weight proteins with a high affinity for heavy metal ions such as zinc, copper, cadmium, and platinum. Immunohistochemically detectable MT overexpression has been demonstrated in a variety of cancers, especially breast carcinoma. In this study, the immunohistochemical expression of MT in normal cervical squamous epithelia, cervical intraepithelial neoplasms (CINs), and invasive cervical squamous carcinomas was investigated. Immunohistochemical staining for proliferating cells using the MIB1 antibody was also performed. In normal squamous epithelia (n = 31), positive staining with MT was confined to basal and parabasal cells. In cases of koilocytosis (n = 14) and CIN I (n = 10), staining was also largely confined to basal and parabasal cells, with only occasional cases of CIN I exhibiting positivity within higher cell layers. Cases of CIN II (n = 14) showed positive staining largely confined to basal and parabasal cells, with staining of higher cell layers in a few cases. In the majority of cases of CIN III (n = 29), there was diffuse positive staining throughout the full epithelial thickness and, in almost all cases, positive staining was present above the basal and parabasal layers. Positive staining was present in 19 of 21 invasive squamous carcinomas. With MIB 1, positivity was confined to the parabasal layer in normal squamous epithelia. In cases of CIN, positive cells were present in progressively higher cell layers, in accordance with the grade of CIN. There was widespread positive staining in all cases of invasive squamous carcinoma. Overexpression of MT, demonstrated immunohistochemically, is associated with CIN III and invasive cervical squamous carcinoma, lesions which exhibit the highest proliferative activity, as shown by MIB1 immunostaining. MT overexpression in cervical squamous lesions appears to occur at some point along the spectrum of high grade CIN and may be related to cell proliferation.

Antigens, Nuclear↗
PubMed1998

Regulation of expression of the erythropoietin gene.

Erythropoietin, a hormone produced in the adult kidney, controls erythrocyte production. In response to ischemic or hypoxic hypoxia, the level of expression of the gene increases markedly. We have a limited understanding of the factors governing the tissue specificity of erythropoietin gene expression but considerable progress has been made toward understanding the mechanisms that increase erythropoietin gene expression in response to hypoxia. An increase in transcription occurs, mediated (at least in part) by formation of a heterodimeric DNA binding complex termed hypoxia inducible factor 1. Transcriptional regulation mediated by this complex has now been shown to modulate the expression of a number of other genes in a wide range of cell types.

Animals↗
PubMed1998

Immunohistochemical staining of normal, hyperplastic, and neoplastic adrenal cortex with a monoclonal antibody against alpha inhibin.

AIMS: To investigate the immunohisto-chemical staining of normal, hyperplastic, and neoplastic adrenal cortex with a monoclonal antibody against alpha inhibin. Also, to determine whether immunostaining with this antibody is useful in differentiating between adrenal cortical neoplasms and other tumours involving the adrenal gland that might mimic them. METHODS: Normal adrenal tissue (n = 20) and specimens from cases of adrenal hyperplasia (n = 13), adrenal cortical adenoma (n = 15), adrenal cortical carcinoma (n = 4), phaeochromocytoma (n = 8), and adrenal metastatic tumour (n = 7) were stained with a monoclonal antibody against the alpha subunit of human inhibin. RESULTS: Positive staining with the anti-alpha inhibin monoclonal antibody was seen in all normal adrenal glands. Immunoreactivity was largely confined to the inner cell layers of the adrenal cortex, with no staining of the adrenal medulla. All hyperplastic adrenal glands and adrenal cortical adenomas and carcinomas were also immunoreactive. The other tumours studied were negative. CONCLUSIONS: There is consistent immunoreactivity with the anti-alpha inhibin monoclonal antibody in normal adrenal cortex and in hyperplastic and neoplastic adrenal cortical lesions. In the normal adrenal cortex, positive staining is mainly confined to the zona reticularis. Other neoplasms involving the adrenal gland are negative. Immunohistochemical staining with anti-alpha inhibin monoclonal antibody, performed as part of a panel, may prove to be of value in the distinction between adrenal cortical carcinoma and phaeochromocytoma or metastatic tumour.

Adrenal Cortex↗
PubMed1998

Detection of chromosomal numerical abnormalities in clinical breast tumour fine-needle aspirations by fluorescence in situ hybridisation (FISH): refinement of a method.

This study sought to refine a fluorescence in situ hybridisation (FISH) technique for the study of numerical chromosome aberrations in cells recovered from breast tumours by fine-needle aspiration (FNA). Such techniques have been used to study numerical aberrations of chromosomes from tumours from many sites. This technique is intended for use in a routine cytopathology laboratory, and no specialised cytogenetics knowledge is necessary. Slide preparation, slide and probe denaturation, and stringency conditions were investigated. We found that the simplest slide preparation technique (direct smears) gave the best results. No difference was seen when slide and probe were denatured together or separately. Stringency conditions must be adapted to suit particular probes. Study of numerical chromosomal changes may help determine their significance in the clinical progression of the disease. Such changes may prove to have prognostic significance and therefore influence treatment of breast cancer. FISH on interphase cells is a technically straightforward, reproducible technique, suited to the study of numerical chromosome aberrations in tumour cells. The method has the potential for use in the study of malignant cells from sites other than breast, including ovary, prostate, lung and bladder.

Biopsy, Needle↗
PubMed1997

Immunohistochemical staining of ovarian granulosa cell tumors with monoclonal antibody against inhibin.

Inhibin is a peptide hormone produced by ovarian granulosa cells and by granulosa cell tumors. Serum inhibin measurements have been used as a biochemical marker of the presence or progression of ovarian granulosa cell tumors and their metastases. In the current study, an antibody against the alpha-subunit of human inhibin was used to stain 16 cases of ovarian adult granulosa cell tumors, 15 cases of other ovarian sex cord-stromal tumors, and 51 cases of a range of ovarian and extraovarian neoplasms, many of which may mimic granulosa cell tumor. There was diffuse strong cytoplasmic staining of all cases of adult granulosa cell tumor. Diffuse positive staining also was observed in all Leydig cell tumors, and there was focal staining in a proportion of fibrothecomas. There was focal weak staining of one case of ovarian clear cell carcinoma but no staining of other ovarian and extraovarian neoplasms. Immunohistochemical staining with antibodies against inhibin is of value in the diagnosis of granulosa cell tumor and in the distinction of this neoplasm from others that may mimic it. The antibody also may be useful for the confirmation of late metastasis of granulosa cell tumor, especially when the previous history is not known.

Female↗
PubMed1997

Immunohistochemical staining of hepatocellular carcinoma with monoclonal antibody against inhibin.

Inhibin is a peptide hormone produced by ovarian granulosa cells. During a recent study investigating the immunohistochemical staining of ovarian granulosa cell tumours and other neoplasms with an anti-inhibin monoclonal antibody, we identified strong cytoplasmic staining of hepatocytes. In the present study we investigated the immunostaining of hepatocellular carcinoma and other neoplasms involving the liver with anti-inhibin to determine whether the antibody may be of value in the differential diagnosis of hepatic neoplasms. Immunostaining for alpha-fetoprotein was also performed. With anti-inhibin there was positive, generally strong, cytoplasmic staining of 17 of 19 cases of hepatocellular carcinoma, including the pleomorphic and glandular variants. There was positive staining of six of 20 cases of adenocarcinoma. In these, positive staining was generally focal, of weak intensity and involved the luminal surface of neoplastic glands. There was no staining of five cases of neuroendocrine tumour. There was positive staining for alpha-fetoprotein in 13 of 19 cases of hepatocellular carcinoma and in two of 20 cases of adenocarcinoma but no staining of neuroendocrine tumours. Immunostaining with anti-inhibin antibody may be of value in the differentiation of hepatocellular carcinoma from other neoplasms involving the liver. The antibody is a more sensitive, but less specific, immunohistochemical marker for hepatocellular carcinoma than is alpha-fetoprotein.

Adenocarcinoma↗