Search PubMed⌕ Search

Biomedical subjects

P Maxwell

Publications and source records attributed to P Maxwell.

At least 73 records · Page 4Linked to original sources
PubMed1997

Immunohistochemical detection of p53 and bcl-2 proteins in neoplastic and non-neoplastic endocervical glandular lesions.

The study examines p53 and bcl-2 protein expression in a variety of neoplastic and non-neoplastic endocervical glandular lesions. Immunohistochemical staining, using monoclonal antibodies against p53 (DO-7) and bcl-2, was performed on archival paraffin-embedded tissue following microwave antigen retrieval. With DO-7 there was positive nuclear staining in 23/33 cases of adenocarcinoma, 2/10 adenocarcinoma in situ, 2/10 tubo-endometrial metaplasia, 1/10 microglandular hyperplasia, and 1/17 normal endocervix. With adenocarcinoma in situ and non-neoplastic lesions, positive staining was confined to scattered cells. Nine of 23 positive cases of adenocarcinoma showed widespread staining. With anti-bcl-2 antibody, there was positive cytoplasmic staining in 9/33 cases of adenocarcinoma, 0/10 adenocarcinoma in situ, 7/10 tubo-endometrial metaplasia, 1/10 microglandular hyperplasia, and 0/17 normal endocervix. Five of nine positive adenocarcinomas showed widespread staining. There was widespread positive staining for bcl-2 in six of seven positive cases of tubo-endometrial metaplasia. The results indicate that p53 protein expression is frequent in endocervical adenocarcinoma and suggest that mutation of the p53 gene may be important in the evolution of some cases of endocervical adenocarcinoma. Scattered p53-positive cells may be seen in endocervical adenocarcinoma in situ and in non-neoplastic endocervical glandular lesions, the significance of which is uncertain. Bcl-2 protein expression is seen in a proportion of endocervical adenocarcinomas and may play a role in the evolution of these tumors through inhibition of apoptosis. Widespread positivity for bcl-2 protein is seen in most cases of tubo-endometrial metaplasia, suggesting that this type of metaplastic epithelium may represent an unusually stable population of cells.

Adenocarcinoma↗
PubMed1997

A comparison of three standard methods of identifying mast cells in endobronchial biopsies in normal and asthmatic subjects.

Reported mast-cell counts in endobronchial biopsies from asthmatic subjects are conflicting, with different methodologies often being used. This study compared three standard methods of counting mast cells in endobronchial biopsies from asthmatic and normal subjects. Endobronchial biopsies were obtained from atopic asthmatic subjects (n = 17), atopic nonasthmatic subjects (n = 6), and nonatopic nonasthmatic control subjects (n = 5). After overnight fixation in Carnoy's fixative, mast cells were stained by the short and long toluidine blue methods and antitryptase immunohistochemistry and were counted by light microscopy. Method comparison was made according to Bland & Altman. The limits of agreement were unacceptable for each of the comparisons, suggesting that the methods are not interchangeable. Coefficients of repeatability were excellent, and not different for the individual techniques. These results suggest that some of the reported differences in mast-cell numbers in endobronchial biopsies in asthma may be due to the staining method used, making direct comparisons between studies invalid. Agreement on a standard method is required for counting mast cells in bronchial biopsies, and we recommend the immunohistochemical method, since fixation is less critical and the resultant tissue sections facilitate clear, accurate, and rapid counts.

Adolescent↗
PubMed1996

Three-dimensional reconstruction of perineural invasion in carcinoma of the extrahepatic bile ducts.

Three-dimensional (3D) reconstruction can be used to study the structural relationships between various tissue components and can help in the understanding of disease processes. Examples of perineural invasion have been reconstructed in two cases of adenocarcinoma of the extrahepatic bile duct. Ninety-six serial 5 microns sections were taken from both cases stored on file and 3D images were constructed using a Kontron VIDAS image analysis system. Both cases showed continuity of tumour cells within the perineural space. The isolated islands of malignant glands seen by conventional microscopy were shown to be in continuity with larger tumour cell masses via a complex branching network. In addition, direct continuity was demonstrated between malignant glands within the perineural space and those within the surrounding stromal tissue. During growth, the tumour appeared to have followed the plane of least resistance, although the availability of the perineural space may itself have been shaped by pressure effects and/or proteolytic enzyme secretion. Three-dimensional reconstruction of perineural invasion in adenocarcinoma of the extrahepatic bile ducts shows the value of this technique in demonstrating the structural relationships between the tumour and the host nerve bundle.

Adenocarcinoma↗
PubMed1996

T-cell-rich histiocyte-rich B-cell lymphoma of parotid gland.

We describe a malignant lymphoma of the parotid gland arising in a patient with Sjögren's syndrome. Diagnosis was established on needle biopsy which showed a mixed population of lymphoid cells. Immunohistochemistry revealed B-lymphoid cells, T-lymphoid cells and histiocytes. Clonal immunoglobulin heavy chain gene rearrangement was demonstrated using the polymerase chain reaction. Within the confines of the small biopsy, the lesion qualifies for the designation T-cell-rich histiocyte-rich B-cell lymphoma. The value of molecular techniques in the diagnosis of malignant lymphoma on limited tissue samples is highlighted by this case.

Aged↗
PubMed1996

The immunophenotype of human decidua and extra-uterine decidual reactions.

Decidua associated with products of conception from intra-uterine and extra-uterine gestations and decidualized tissue from the appendix, cervix and Fallopian tube were studied using a panel of antibodies and antisera. Immunolocalization of vimentin and desmin intermediate filament proteins and of alpha-1-antitrypsin and alpha-1-antichymotrypsin was identified in most of the 43 cases studied. Placental alkaline phosphatase, beta human chorionic gonadotrophin, cytokeratin, smooth-muscle actin and leukocyte markers (CD3, CD20, CD68) were also expressed in some cases. Occasional cases reacted for CD45 and S-100 protein. Similar reaction profiles were obtained at both intra-uterine and extra-uterine sites. The results show that extra-uterine mesenchymal cells which have undergone a decidual reaction correspond closely to their counterparts in the endometrial stroma. Since positive immunostaining within decidual cells for cytokeratins, placental alkaline phosphatase and beta human chorionic gonadotrophin indicates that trophoblastic cells are not exclusively recognized by these antibodies, their use does not permit the confident diagnosis of an intra-uterine gestation.

Alkaline Phosphatase↗
PubMed1996

Monoclonal antibody MIB1 in the assessment of cervical squamous intraepithelial lesions.

The aims of the study were to assess patterns of cell proliferation, using the monoclonal antibody MIB1, in a variety of non-neoplastic and neoplastic cervical squamous intraepithelial lesions. We also wished to determine whether this antibody is of value in the discrimination of different grades of cervical intraepithelial neoplasia (CIN) and in the distinction of CIN from non-neoplastic lesions that may histologically mimic CIN. Tissue sections of formalin-fixed, paraffin-embedded cervical colposcopic biopsies were stained immunohistochemically with MIB1 after microwave heating. Normal ectocervix and cervical specimens exhibiting immature squamous metaplasia, koilocytosis, CIN grades I, II, and III, and atrophic squamous epithelium were studied. In normal ectocervix, MIB1-positive cells were confined almost exclusively to the parabasal cell layer. Increased expression was seen in cases of koilocytosis and CIN, positive staining being present in progressively higher layers of epithelium in accordance with the degree of CIN. In immature squamous metaplasia, positive staining was generally confined to the parabasal layer with occasional scattered positive cells in higher layers of epithelium. There was little or no staining of atrophic squamous epithelium. The study confirms that proliferating cells, as demonstrated by MIB1 immunostaining, are found at progressively higher levels in cervical squamous epithelia from normal to koilocytosis to CIN grades I, II and III. Immunostaining with MIB1, which can be easily performed on routinely processed tissues, is of potential value as an adjunct to histology in the grading of CIN and the distinction of CIN from non-neoplastic lesions that may mimic CIN.

Antibodies, Monoclonal↗
PubMed1995

Two cases of infected atherosclerotic aneurysms and a comparison with infective endocarditis.

Two cases of infected atherosclerotic aneurysms thought to have arisen following haematogenous seeding of atheromatous lesions are described. Although infective endocarditis also arises by the haematogenous route, there are striking contrasts in both the range and therefore likely source of organisms, together with a perceived difference in the rate of blood-culture positivity. This case report provides a focus for discussion of these observations.

Aged↗
PubMed1995

Evaluation of the thoracic and lumbar spine after blunt trauma.

BACKGROUND: Routine performance of thoraco-lumbar (TL) spinal radiology in patients with blunt trauma is controversial. PATIENTS AND METHODS: To establish indications for radiologic screening of the TL spine, a retrospective review of 344 patients who had radiologic evaluation of the spine was performed. RESULTS: Forty-seven patients had abnormalities detected on radiologic evaluation. One hundred eighty-six patients had at least one clinical finding suggestive of injury. Thirty-two had abnormal radiographs. Thirteen of these abnormalities represented old or minor fractures and were not treated. Nineteen patients had injuries requiring treatment. Two patients were treated with activity restriction, 12 with a back brace, 4 with operative fixation, and 1 patient died prior to operation. Of the 129 patients who were awake, alert, and without clinical evidence of injury, 10 had abnormal radiologic studies. Three patients had old fractures, 4 had transverse process fractures, and 3 had spondylolisthesis. None of these patients required treatment. Twenty-nine patients had equivocal clinical examinations primarily due to altered levels of consciousness. Five patients had abnormal radiologic studies, 3 of whom required treatment. Three factors associated with the occurrence of TL spine injury were identified: an Injury Severity Score > or = 15, a positive clinical examination, and a fall of > or = 10 feet. CONCLUSIONS: These data suggest that patients who are awake, alert, and with no clinical evidence of injury do not require radiologic study of the TL spine. Patients with equivocal or positive clinical findings or with altered levels of consciousness should have complete TL spine evaluation.

Adult↗
PubMed1995

Monoclonal antibodies Ki-67 and MIB1 in the distinction of tuboendometrial metaplasia from endocervical adenocarcinoma and adenocarcinoma in situ in formalin-fixed material.

This study was undertaken to determine whether immunostaining with the monoclonal antibodies Ki-67 and MIB1 is of use in the distinction of tuboendometrial metaplasia from endocervical adenocarcinoma and adenocarcinoma in situ (AIS) on formalin-fixed, paraffin-embedded tissue. Tissue sections from 100 cases (52 normal endocervix, 27 endocervical tuboendometrial metaplasia, eight endocervical AIS, 13 endocervical adenocarcinoma) were stained with Ki-67 and MIB1 after microwave pretreatment in citrate buffer. Ki-67 and MIB1 labelling indices (LIs) were calculated in each case by determining the percentage of positive-staining nuclei. Five hundred nuclei were counted in each case. Significant differences in Ki-67 and MIB1 LIs existed between the adenocarcinoma group and the tuboendometrial metaplasia group and between the AIS group and the tuboendometrial metaplasia group. No significant differences existed between the adenocarcinoma and AIS groups. Over all groups, the Ki-67 LI was consistently lower than the MIB1 LI. The results indicate that immunohistochemical staining with Ki-67 and MIB1 may be of use in the often difficult histological distinction of tuboendometrial metaplasia from malignant endocervical glandular lesions.

Adenocarcinoma↗
PubMed1995

Cytokeratin intermediate filament expression in benign and malignant breast disease.

AIM: To carry out a comprehensive study of cytokeratin expression in benign and malignant breast epithelium and breast myoepithelial cells; to examine changes in the cytokeratin profile in malignant and benign epithelium and in carcinomas of increasing histological grade. METHODS: Frozen sections from fibroadenomas (19 cases), fibrocystic disease (19 cases), and infiltrating ductal (68 cases), lobular (seven cases), and mucinous carcinomas (three cases) were examined using a panel of monoclonal antibodies. RESULTS: The luminal epithelium in all fibroadenomas and all cases of fibrocystic disease, as well as tumour cells in most carcinomas, reacted with the specific antibodies to cytokeratins 7, 8, 18, and 19 and to antibodies which included these cytokeratins in their specificities (Cam 5.2, AE1, AE3, RCK102, and LP34). In a few ductal carcinomas none of the tumour cells reacted for cytokeratins 7, 8, or 18. Three ductal carcinomas expressed cytokeratin 14. Only occasional cases expressed cytokeratins 3, 4, 10, and 13. Antibodies which included cytokeratins 5 and 14 in their specificities detected myoepithelial cells less efficiently than antiactin antibodies. CONCLUSION: The cytokeratin profiles in the luminal epithelium in benign breast disease and in tumour cells in most carcinomas are similar in most cases. Some carcinomas, however, are negative for cytokeratins 7, 8, or 18. This may provide a means of predicting the biological behaviour of a histologically borderline lesion.

Antibodies, Monoclonal↗
PubMed1995

Vimentin and cytokeratin expression in nodular hyperplasia and carcinoma of the prostate.

AIM: To assess the value of vimentin and cytokeratin (CK) intermediate filament proteins (IFPs) in distinguishing between nodular hyperplasia and carcinoma of the prostate and in predicting prognosis in prostatic cancer. METHODS: Fifteen carcinomas and 49 cases of nodular hyperplasia were studied using frozen sections and monoclonal antibodies to CK and vimentin IFPs. RESULTS: There was no statistically significant difference in vimentin expression between nodular hyperplasia and carcinoma. The luminal epithelium in both also reacted with antibodies which detect CK8, 18 and 19. CK 7 expression was found in 57% of cases of nodular hyperplasia and was not identified in any carcinoma. There was a reaction with antibodies to CK1, 2, 3, 4, 10, 11, and 13 in only a minority of cases. There was no statistically significant difference in vimentin and CK reactivity in high and low grade carcinomas. CONCLUSION: Neither vimentin nor CK expression assists in establishing whether a prostatic lesion is benign or malignant or in predicting the biological behaviour of a prostatic carcinoma.

Diagnosis, Differential↗
PubMed1995

Immunohistochemical staining of plastic embedded bone marrow trephine biopsy specimens after microwave heating.

AIMS: To investigate (1) whether adequate immunohistochemical staining can be achieved on sections cut from plastic embedded bone marrow trephine biopsy specimens after microwave heating in citrate buffer; and (2) whether this immunohistochemical staining is comparable with that achieved on routine sections cut from paraffin wax embedded trephine biopsy specimens after decalcification procedures. METHODS: Sixty five consecutive bone marrow trephine biopsy specimens of more than 1 cm in length were divided transversely into two equal parts. One part was processed in paraffin wax followed by decalcification. The other part was embedded in the epoxyresin Polarbed 812 followed by the cutting of 1 micron sections. Both parts underwent immunohistochemical staining by an identical panel of antibodies. With Polarbed 812 plastic embedded sections, microwave heating in citrate buffer was undertaken before the application of antisera. RESULTS: On sections cut from plastic embedded material, immunohistochemical staining was generally satisfactory, easy to interpret and comparable with that achieved with paraffin wax embedded material. Exceptions were antibodies to neutrophil elastase and CD61 where immunostaining was consistently negative on plastic embedded sections. Immunohistochemical staining for CD20 was consistently more reliable on plastic embedded sections. CONCLUSIONS: The results provide evidence that, with few exceptions, satisfactory immunohistochemical staining is possible on plastic embedded bone marrow trephine biopsy specimens after microwave heating in citrate buffer. This, combined with the advantage of superior cellular morphology with semi-thin (1 micron) sections of plastic embedded material, make such embedding procedures the preferred method for the processing of bone marrow trephine biopsy specimens.

Antibodies, Monoclonal↗
PubMed1994

Cytosolic phospholipase A2 gene expression in rat mesangial cells is regulated post-transcriptionally.

Cytosolic phospholipase A2 (cPLA2) is thought to be the rate-limiting enzyme in the arachidonic acid/eicosanoid cascade. The ability of various agonists to increase steady-state cPLA2 mRNA levels has previously been reported. The current study delineates the contributions of transcriptional and post-transcriptional processes to the regulation of cPLA2 gene expression in response to a variety of agonists in cultured rat glomerular mesangial cells. Epidermal growth factor, platelet-derived growth factor, serum and phorbol myristate acetate all increase the half-life of cPLA2 mRNA transcripts, indicating a role for post-transcriptional modulation of gene expression. The presence of three ATTTA motifs in the 3' untranslated region (3'UTR) of the rat cPLA2 cDNA is ascertained. Heterologous expression of chimeric constructs with different 3'UTRs ligated into the 3' end of the luciferase coding region reveals that the presence of the cPLA2 3'UTR results in reduced luciferase activity compared with constructs without the cPLA2 3'UTR. Furthermore, the luciferase activity in the constructs with the cPLA2 3'UTR is increased in response to the same agonists which stabilize endogenous cPLA2 mRNA. A negligible effect of these agonists on transcriptional control of cPLA2 is evident using promoter-reporter constructs expressed in transient and stable transfectants. Taken together, these results indicate predominant post-transcriptional regulation of cPLA2 mRNA levels.

Animals↗
PubMed1994

Isolation of promoter for cytosolic phospholipase A2 (cPLA2).

Cytosolic phospholipase A2 (cPLA2) releases arachidonic acid from membrane phospholipids and is believed to be the rate-limiting enzyme in the arachidonic acid pathway. We report herein the isolation of a 3 kb fragment of rodent genomic DNA containing part of the first intron, the first exon and 5'-flanking sequence. The start site of transcription was mapped by 5'-rapid amplification of cDNA ends and corroborated by ribonuclease protection assay. The gene has a TATAless promoter with no classical Sp1 binding sites or initiator element. A microsatellite series of CA repeats was noted in the 5'-flanking region of both the rodent and human promoters. Deletion constructs have been analysed for luciferase activity and confirmed promoter activity.

Amino Acid Sequence↗
PubMed1994

Reduced phospholipase A2 activity is not accompanied by reduced arachidonic acid release.

Arachidonic acid release in cells highly over expressing cytosolic phospholipase A2 has been attributed to mitogen-activated protein kinase phosphorylation of cytosolic phospholipase A2 on serine-505. To investigate the role of cytosolic phospholipase A2 in cellular physiology, we attempted to inhibit cytosolic phospholipase A2 in the intact cell employing an antisense RNA strategy. Swiss 3T3 cells were stably transfected with an antisense cytosolic phospholipase A2 expression vector. A clone of cells with reduced immunodetectable cytosolic phospholipase A2, compared to a vector transfected cell line, was identified by Western blotting and a corresponding decrease in phospholipase A2 activity was confirmed by enzymatic assay in cell free extracts. However, arachidonic acid release from intact cells in response to agonists was not different between antisense and control cell lines. Thus, arachidonic acid release in intact cells with decreased cytosolic phospholipase A2 activity is likely to be modulated by rate limiting factors that are extrinsic to cytosolic phospholipase A2.

3T3 Cells↗
PubMed1994

p53 expression, mutation, and allelic deletion in ovarian cancer.

The aim of this investigation was to study the prevalence of p53 gene mutations and allelic deletions in ovarian cancer and the relationship between these events and p53 expression. Genomic p53 was amplified by the polymerase chain reaction (PCR) from paraffin-embedded sections of tumour and non-tumour tissue. Exons 5-9 were screened for mutation using non-isotopic single-strand conformation polymorphism (SSCP) analysis. Allelic deletions at a sequence polymorphism in exon 4 were studied for loss of heterozygosity (LOH) by restriction analysis and by SSCP. p53 expression was detected by immunohistochemistry with the p53 antibodies CM1 and Do7. Of 44 cases, ten (23 per cent), including a mucinous tumour of low malignant potential, showed mutations. There was a statistically significant correlation between p53 mutation and expression (P < 0.01) but seven cases showed discordance. Of 18 informative cases, eight (44 per cent) demonstrated LOH. Mutations were identified in three of the informative cases, two of which also had LOH. The remaining case showed mutations in two amplicons. p53 dysfunction, as indicated by mutation, deletion, or increased expression, is common in ovarian cancer. There is an association between these molecular events but the exact mechanisms of p53 inactivation remain to be elucidated.

Alleles↗
PubMed1993

Carcinoembryonic antigen (CEA) in benign and malignant epithelium of the gall bladder, extrahepatic bile ducts, and ampulla of Vater.

Carcinoembryonic antigen (CEA) has been reported in benign and malignant epithelium of the gall bladder, although cross-reactivity with CEA-related antigens cannot be excluded. We have investigated the immunoreactivity of three monoclonal and two polyclonal antisera to CEA in benign and malignant epithelium of the gall bladder, extrahepatic bile ducts, and ampulla of Vater. The results varied with the antisera, due to cross-reactivity with CEA-related antigens and according to the epitope specificities. Little CEA was found in benign epithelium using monoclonal antisera or following absorption of a polyclonal antiserum from Dako with human liver powder. The latter was the most reliable at detecting malignant epithelium of the gall bladder and extrahepatic bile ducts. All antisera showed equal immunoreactivity in tumours of the ampulla of Vater. The differences seen in the immunoreactivities between tumours of the upper and lower extrahepatic biliary tract probably indicate a variation in the occurrence of CEA epitopes.

Adult↗