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Biomedical subjects

M Leader

Publications and source records attributed to M Leader.

At least 91 records · Page 5Linked to original sources

Review of an Irish cervical smear service.

Cervical cytology material from 5,815 women who presented to General Practitioners throughout Ireland for routine cervical smears were referred to our Pathology Laboratory. The smears were reviewed retrospectively in order to report on the incidence of dyskaryosis and other abnormalities diagnosed on cervical cytology. Evidence of dyskaryosis was found in a total of 2.2% and "borderline" changes in a total of 0.3% of smears. Cytology and subsequent histology were compared in cases of significant cervical intraepithelial neoplasia. Comparison in cases of moderate and severe dyskaryosis showed precise correlation between the diagnosis of cervical intraepithelial neoplasia on biopsy and its prediction on cytology in 30 of 33 cases. Over a third of women screened were in their 4th decade and the highest incidence of dyskaryosis was in this age group. Only 10% of those screened were 50 years or over and a third were aged 40 years and over. These facts are of relevance with regard to the problem of targeting the population at risk in the long term planning of routine cytology screening services in this country.

Adolescent↗

Ploidy of smooth muscle tumours: retrospective image analysis study of formalin fixed, paraffin wax embedded tissue.

The feasibility of using an image analyser, the CAS 100, to assess the ploidy of smooth muscle tumours on formalin fixed paraffin wax embedded tissue was assessed. Various different methods of assessment were compared. A paraffin wax block of 15 leiomyomata and 13 leiomyosarcomata yielded serial sections of 3 microns, 5 microns, and 7 microns and a cytospin preparation (from a 50 micron section). Sections and cytospin preparations were stained with Feulgen and quantified using the CAS 100. The suitability of lymphocytes, previously suggested to be unsuitable as control cells in tissue sections due to the compact nature of their DNA, was assessed in sections and cytospin preparations and compared with endothelial cells, the standard alternative, on the same slide. Despite having a mean nuclear area of only 18.5 microns 2 in sections lymphocytes had a similar diploid peak--that is, 4.1 pg--to endothelial cells (mean nuclear area 39 microns 2). A comparison of 3 microns, 5 microns, and 7 microns sections showed 5 microns to be the optimal thickness. Cytospin preparations yielded histograms of superior quality than those from tissue sections. All 15 leiomyomata had a 5C exceeding rate of less than 0.3%. Ten of 11 histologically malignant tumours had a 5C exceeding rate of more than 5% (mean 14%) in sections and cytospins. Two leiomyosarcomata that had arisen in the lower gastrointestinal tract had a mitotic rate of less than or equal to 1/10 per high power fields and yielded histograms similar to those of the leiomyomata. It is concluded that formalin fixed, paraffin wax embedded tissue can be used for DNA quantification by image analysis; that tissue sections yield poorer results than cytospin preparations; that lymphocytes are reliable control cells in cytospin preparations; and that a population of cell greater than 5C is seen in 90% of leiomyosarcomata.

Cell Separation↗

Myoglobin: an evaluation of its role as a marker of rhabdomyosarcomas.

Tumour markers now have an established role in tumour diagnosis and patient management. However, antibodies used to detect these tumour markers have in some instances proved unreliable, with a low rate of sensitivity and specificity. In this study we wished to evaluate the role of a commercial antibody to myoglobin as a marker of rhabdomyosarcomas. The purpose of this investigation was to assess the sensitivity and specificity of myoglobin antiserum as a marker of rhabdomyosarcomas. This was performed by reacting a large number of tumours (sarcomas, carcinomas and melanomas) with a polyclonal anti human myoglobin antiserum. Staining was demonstrated in 60% of rhabdomyosarcomas. Only two tumours from a total of 226 non-skeletal muscle tumours showed a positive reaction (0.88%). One was a leiomyosarcoma and the other had been classified as an undifferentiated sarcoma but a rhabdomyosarcoma was included in its differential diagnosis. It is of interest that both had been earlier irradiated. This antiserum was therefore a specific but not a very sensitive tumor marker. Its rate of staining of rhabdomyosarcomas is compared with the results in the literature. A great disparity is found and the reasons for this are discussed.

Adolescent↗

Synovial sarcomas. True carcinosarcomas?

The histogenesis of synovial sarcomas remains controversial. An origin from epithelium, synovium, or synovial-related cells and neural tissue has been advanced. Using a combination of a cytokeratin (epithelial marker) antibody and a vimentin (mesenchymal marker) antibody, this study suggests that a synovial sarcoma might be regarded as a carcinosarcoma. It also highlights the diagnostic utility of those antibodies in the diagnosis of synovial sarcomas.

Carcinosarcoma↗

Desmin: its value as a marker of muscle derived tumours using a commercial antibody.

This study examined the staining reactions of a commercially available anti desmin antibody in 192 soft tissue sarcomas, 30 carcinomas and 22 malignant melanomas. Only 63% of rhabdomyosarcomas and 50% of leiomyosarcomas showed a positive reaction. Three non muscle sarcomas also reacted with the antibody. No positivity was seen amongst the carcinomas or the melanomas. These results do not compare favourably with the documented results of non commercial desmin antibodies in the literature. The most likely cause of the discrepancy in the varying results is the differing source of the antibody.

Adolescent↗

Phyllodes tumour of the breast: response to radiotherapy.

A 47 year old woman presented with a rapidly growing recurrence in the chest wall following simple mastectomy for a malignant phyllodes tumour of the breast. Radical megavoltage irradiation led to histologically confirmed complete regression of her tumour.

Breast↗

Anti-alpha 1-antichymotrypsin staining of 194 sarcomas, 38 carcinomas, and 17 malignant melanomas. Its lack of specificity as a tumour marker.

A polyclonal commercially available antiserum to alpha 1-antichymotrypsin (alpha 1ACT) was reacted with 194 sarcomas, 38 carcinomas, and 17 malignant melanomas; 61 of 194 sarcomas, 14 of 38 carcinomas, and 10 of 17 malignant melanomas reacted positively. Thirteen categories of sarcomas were examined. All but one group (haemangiopericytomas) showed positively staining tumour cells. Malignant fibrous histiocytomas, angiosarcomas, and Kaposi's sarcomas showed positive staining in over 70% of tumours. All categories of carcinomas examined, with the exception of transitional cell carcinomas, stained positively. The results of this study suggest that the use of alpha 1ACT antiserum is of little value in the differential diagnosis of either sarcomas or carcinomas, nor can it be used as a specific histiocytic marker.

Antibodies↗

Vimentin: an evaluation of its role as a tumour marker.

In this study we examined 198 sarcomas, 38 carcinomas, 13 'tumours with a spindle cell component' and 22 malignant melanomas with a commercial monoclonal vimentin antibody. All histopathological material was formalin fixed and paraffin embedded. The results show this antibody to be a sensitive and specific marker of mesenchymal derivation or differentiation. It is a useful tool in separating sarcomas from most carcinomas, and in separating malignant melanomas from carcinomas. When used in combination with a cytokeratin antibody it identifies carcinosarcomas and synovial sarcomas.

Antibodies, Monoclonal↗

Bilateral submandibular gland lymphoma in Sjögren's syndrome.

Salivary gland lymphoma is associated with Sjögren's syndrome. A case of bilateral submandibular gland and sublingual gland lymphoma, arising in Sjögren's syndrome, is presented. A lymphoma involving more than one salivary gland may occur in Sjögren's syndrome, and there is an increased risk of developing an extrasalivary lymphoma.

Female↗

Focal loss of anterior horn cells in the cervical cord in motor neuron disease.

In a three-dimensional study of the distribution of anterior horn cells in the C8 segment of the human spinal cord we have recognized lateral and medial zones of motor neuron groupings, but have not been able to recognize subgroups of neurons within these groupings resembling the anatomical columns described by earlier investigators. This observation does not invalidate the concept of functional groupings within these anterior horn cell pools. In studies of the same segment in cords obtained at autopsy from patients with motor neuron disease, zones of focal loss of motor neurons were identified, without consistent severity or distribution at different sectional levels. These findings imply varying resistance to the disease in different pools of motor neurons.

Aged↗

Staining for factor VIII related antigen and Ulex europaeus agglutinin I (UEA-I) in 230 tumours. An assessment of their specificity for angiosarcoma and Kaposi's sarcoma.

In this study we examined the staining reactivity of commercially available antisera to factor VIII related antigen (F VIII RAg) and Ulex europaeus agglutinin I (UEA-I) on sections from 230 formalin fixed paraffin embedded tumours. These included 196 sarcomas, 20 carcinomas and 14 angiomas. All angiomas showed positive staining for F VIII RAg; all carcinomas showed negative staining; the vasoformative areas of all angiosarcomas stained positively but only four of six angiosarcomas showed positive staining of their solid areas; of seven Kaposi's sarcomas, all showed positive staining of vessels and six showed positive staining of the spindle cell component. In the remaining 181 non-vascular sarcomas there was a false positive result in four tumours (2.2%), three of which had a history of irradiation. Pre-radiotherapy biopsies of these three tumours stained negatively with anti-F VIII RAg. UEA-I was demonstrated in all the angiomas studied, in all angiosarcomas (including the solid components) and in well-formed vessels of all Kaposi's sarcomas, but only in the spindle cell component of 3/6. However, there was an unacceptably high rate of false positive staining amongst the carcinomas and non-vascular sarcomas. In conclusion, F VIII RAg is a specific but not a sensitive marker of angiosarcomas; UEA-I is a sensitive but not a specific marker of angiosarcomas.

Adolescent↗

An analysis of the sensitivity and specificity of the cytokeratin marker CAM 5.2 for epithelial tumours. Results of a study of 203 sarcomas, 50 carcinomas and 28 malignant melanomas.

Two hundred and three sarcomas, 40 carcinomas, 10 carcinomas with spindle cell features, 27 malignant melanomas and one spindle cell melanoma were examined using CAM 5.2, a monoclonal antibody to cytokeratin. This antibody which was prepared against colorectal carcinoma cells and which identifies low molecular weight intermediate filament cytokeratin proteins is suitable for use in formalin fixed, paraffin embedded material. Seventeen of the 203 sarcomas showed positive staining. These included 15/21 synovial sarcomas, 1/5 epithelioid sarcomas and 1/18 malignant neural tumours. Five carcinosarcomas showed positive staining of their epithelial components but negative staining of their spindle cell components; three out of four pure spindle cell carcinomas stained positively; a metastasis from a spindle cell renal carcinoma was negative. A spindle cell thymoma also stained positively. Thirty-seven of the 40 carcinomas stained positively; the three negative carcinomas were a squamous cell carcinoma, a renal cell carcinoma and an oat cell carcinoma. All malignant melanomas were negative. These results are compared with those of other workers and the sensitivity and specificity of CAM 5.2 as an epithelial marker is assessed.

Antibodies, Monoclonal↗

Antineuron specific enolase staining reactions in sarcomas and carcinomas: its lack of neuroendocrine specificity.

A commercially available polyclonal antiserum (Dakopatts) raised against bovine neuron specific enolase (NSE) was reacted with 197 sarcomas, 32 carcinomas, 11 carcinoid tumours and 20 malignant melanomas to assess its specificity for neuroendocrine tumours. All the tumours had been fixed in formalin and embedded in paraffin. Positive tumour cells were found in two of 11 squamous cell carcinomas, one of 11 adenocarcinomas, 10 of 10 oat cell carcinomas, 11 of 11 carcinoid tumours, 16 of 20 malignant melanomas, four of seven clear cell sarcomas, nine of 25 leiomyosarcomas, four of 22 rhabdomyosarcomas, one of seven angiosarcomas and one of 20 synovial sarcomas.

Antibody Specificity↗

A 38 base pair insertion in the pro alpha 2(I) collagen gene of a patient with Marfan syndrome.

Abnormalities in type I collagen have been recognized in a number of connective tissue disorders. In the Marfan syndrome, an autosomal dominant condition producing a generalized abnormality in connective tissue, no consistent abnormality has been identified, although one individual has been found to have an elongated pro alpha 2(I) collagen chain [Byers et al, Proc Natl Acad Sci USA 78:7745, 1981]. To determine the nature of the alteration in the gene that produced this abnormality, we studied the pro alpha 2(I) gene from this individual by genomic blotting and gene cloning. Genomic mapping studies detected no abnormalities. However, analysis of the cloned segment of the pro alpha 2(I) collagen gene from the Marfan individual indicates that the gene contains a 38 base pair insertion in an intron near the collagenase cleavage site. Although the relationship of this insertion to the protein abnormality is unclear, it may be a useful marker for the diagnosis of the Marfan syndrome.

Base Sequence↗