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Biomedical subjects

J M Skinner

Publications and source records attributed to J M Skinner.

At least 37 records · Page 2Linked to original sources
PubMed1989

Calbindin immunoreactivity is a characteristic of enterochromaffin-like cells (ECL cells) of the human stomach.

Immunoreactivity for the calcium binding protein, calbindin D28k has been localized in enterochromaffin-like (ECL) cells of the human stomach. The reactivity was observed with three different antisera, raised against bovine brain, primate brain, and chicken intestinal calbindin. The ECL cells were closed endocrine cells located at the bases of the oxyntic glands. They were not found in other regions of the stomach. No other gastric endocrine cells were reactive with these antisera.

Adult↗
PubMed1989

Development and characterization of primary cultures of smooth muscle cells from the fibromuscular stroma of the guinea pig prostate.

Primary cultures of smooth muscle cells (SMCs) were obtained by a two-step enzymatic digestion of guinea pig prostatic stroma. Ultrastructural morphology and growth characteristics of these cells conformed to those reported for SMCs isolated from vascular and visceral tissue sources. Electron microscopic examination indicated that the cells assumed modified myofibroblastoid features in culture. Microfilaments with associated dense bodies were markedly depleted in cultured smooth muscle cells, in comparison with those of the parent tissue. Cultured cells also possessed increased content of rough endoplasmic reticulum indicating the increased secretory or protein-synthetic capacity of the cells. Immunoperoxidase staining for cytoskeletal markers using monoclonal antibodies to desmin and vimentin supported the ultrastructural observations, suggesting a decline in desmin-staining intermediate filaments during "modulation" to the myofibroblastoid form. Despite this depletion of smooth muscle-specific differentiation markers and reversion to more general mesenchymal properties, the cells retained the ability to contract on challenge with norepinephrine, and grew in the characteristic "hill and valley" pattern on attaining confluence. Inasmuch as the estrogen and androgen receptor expression of the parent stromal tissue is also retained, these primary cell cultures should provide a useful model to study regulation of prostatic development.

Androgens↗
PubMed1989

Steroid hormone and epidermal growth factor receptors in meningiomas.

A prospective study of steroid hormone and epidermal growth factor receptor expression in 57 meningiomas is presented. Scatchard analysis of radioligand binding identified 20% of meningiomas as expressing classical oestrogen receptors (ER) at levels below that normally accepted for positivity, the remainder being negative. ER could not be visualized in any meningioma using immunocytochemistry. Alternatively, 74% of meningiomas demonstrated the presence of progesterone receptors (PR) by Scatchard analysis, the specificity of which could not be attributed to glucocorticoid or androgen receptors. Confirmation of classical PR presence was determined by immunocytochemical staining. The presence of epidermal growth factor receptor (EGFR) was demonstrated in 100% of meningiomas using immunocytochemical staining. These data are reviewed in the context of previously reported results and are discussed in relation to the potential for medical therapy as an adjunct to surgery.

Adult↗
PubMed1989

Expression of MHC class I and class II antigens in colonic carcinomas.

Malignant and non-malignant ('normal') colonic tissues from patients with colonic carcinoma were examined for the expression of MHC class I and class II antigens by immunoenzymatic staining using monoclonal antibodies. The amount of class I antigen as detected by 2 monoclonal antibodies, FMC 16 or W6/32 was clearly diminished in 11 of 14 tumours when compared to the amount present on 'normal' colonic tissue from the same individual. The loss of class I antigen did not correlate with tumour stage or differentiation. The reactivities of FMC 16 and W6/32 with these tissues were not identical, which indicates that the 2 monoclonal antibodies may recognize different epitopes on the HLA class I molecule. Class II antigens were absent from 'normal' colonic epithelium but were present on 20 of 28 tumours, with DR being detected more often than DP, and DQ found only on 4 of 28 tumours. When present, staining for class II antigens was heterogeneous within the tumour, in that all tumour cells did not stain equally. DR and DP antigens were found more often on moderately or poorly differentiated adenocarcinomas and on stage B, C and D tumours in that order of frequency. Thus tumours with a better prognosis were less likely to express DR and DP. The expression of DQ was unrelated to staging or differentiation.

Antibodies, Monoclonal↗
PubMed1988

Production of a polyspecific human monoclonal antibody reacting with an epidermal antigen.

A clone of cells secreting an antibody to an epidermal antigen was generated from a patient with a blistering skin lesion. Although produced by fusion of human lymphocytes to a HAT-sensitive myeloma, this clone of cells did not have characteristics of a hybridoma. A true hybridoma was produced by fusion of this clone to a HATr/ouabain(r) myeloma line. The IgM antibody secreted by this clone reacted with the intercellular region of the epidermis of normal human skin in a manner similar to pemphigus autoantibodies. In addition, in normal human kidney the antibody bound to glomeruli and tubules. It also reacted with an antigen present in the cytoplasm of a wide variety of cell lines including epithelial, lymphoid and myeloid types. No reaction was found with the surface of any of the cell lines, nor with DNA or phospholipid antigens. This monoclonal antibody may define an autoantibody specificity which mediates some autoimmune skin lesions. Its polyspecificity is reminiscent of some other human hybridoma autoantibodies, and its reaction with components of the kidney suggests an alternative pathology for renal disease in such patients.

Antibodies, Monoclonal↗
PubMed1988

Monoclonal alkaline phosphatase-anti-alkaline phosphatase (APAAP) complex: production of antibody, optimization of activity, and use in immunostaining.

A mouse monoclonal antibody, FMC55 (an IgG1), to alkaline phosphatase was prepared and evaluated in immunostaining. Clones producing antibody to alkaline phosphatase were selected using a micro-ELISA which identified antibodies forming active soluble complexes (APAAP) with the enzyme. Conditions that influenced the formation of the complex were investigated by using a quantitative assay in which the complex was captured by a bridging anti-mouse antibody. The ratio of FMC55 to enzyme had a major influence on the activity of the complex. Although all complexes had some activity, those that contained excess antibody had reduced ability to bind to anti-mouse antibody because of competition with excess unlabeled antibody. The optimal complex was formed with 3 micrograms of FMC55 per unit of enzyme. This complex contained neither free enzyme nor free antibody. The molecular weight by gel permeation chromatography was 600,000, giving a composition of two enzyme and two antibody molecules or one enzyme and three antibody molecules. The size of the complex was not altered by adding excess antibody or excess enzyme. Immunoblotting showed that FMC55 bound only to the Mr 140,000 homodimeric form of alkaline phosphatase. The APAAP complex was used in combination with biotin-streptavidin-peroxidase reagent to detect two antigens labeled with two different mouse monoclonal antibodies in the same tissue preparation.

Alkaline Phosphatase↗
PubMed1987

Expression of a Tn-like epitope by carcinoma cells.

A monoclonal antibody, FBT3, was raised against Tn positive erythrocytes and, using immunohistochemistry, fresh and fixed tissues from patients with cancer were studied to detect any expression of a Tn-like epitope. Expression was found in neoplastic cells, usually both in cytoplasm and on cell membranes, from 104 of 147 cases of carcinoma and 1 of 13 cases of lymphoma, but rarely in adjacent, morphologically normal cells. Tn expression was seen in some normal glandular cells but, unlike cancer cells, it was distributed as fine granules in a supranuclear position. Detection of a Tn-like epitope is of theoretical interest and may be of direct diagnostic value.

Animals↗
PubMed1986

Measuring S100 protein and neurone specific enolase in melanocytic tumours using video image analysis.

Using a computed video image analysis system, the staining intensity for both neurone specific enolase (NSE) and S100 protein was measured in sections from 19 malignant melanomas and 16 benign melanocytic lesions. The results of this study confirm previous reports that NSE and S100 protein are useful markers for malignant melanoma. NSE staining intensity in the cases of malignant melanoma was significantly higher than that in benign naevi (p = 0.011). Intensity of staining for S100 protein was not significantly higher in the malignant melanomas. There was, however, a significant S100 gradient when comparing superficial and deep intradermal portions of these tumours (p = 0.003). This feature was not seen in benign naevi. The greatest intensity of S100 protein staining was found in the deeper portions of the malignant melanomas. This gradient difference was not seen with staining for NSE. Although it seems that the overall intensity of staining for NSE is more effective in differentiating between benign and malignant lesions, the difference in staining intensity between the superficial and deep portions of the tumour may be the better indicator of adverse behaviour in lesions in which the diagnosis of malignancy is uncertain.

Humans↗
PubMed1985

A morphometric classification of acute lymphoblastic leukemia in children.

In order to reduce the subjective errors in subtyping leukemic lymphoblasts using the French-American-British (FAB) classification, computer-assisted morphometry was used. Bone marrow smears obtained at diagnosis from 99 children with acute lymphoblastic leukemia (ALL) were analysed by this method and compared with the subjective FAB classification. The results confirm that lymphoblast morphology, as a single variable, is a very significant predictor of survival in ALL. This computer-assisted morphometric analysis would be of great value in large-scale clinical trials in ALL.

Bone Marrow↗
PubMed1985

The ultrastructural immunohistochemistry of oncofoetal antigens in large bowel carcinomas.

Seven large bowel carcinomas were examined by light and electron microscopy for the presence of five oncofoetal antigens. Ultrastructural investigations involved a novel method whereby thick sections of gluteraldehyde-fixed material were cut on a vibratome and then labelled using slight modifications of a standard unlabelled antibody-enzyme (PAP) technique, before further processing. Ultrastructural preservation, staining properties and the retention of antigen activity was seemingly better than that achieved by other investigators. Specific, positive labelling for carcinoembryonic antigen (CEA), colon specific antigen (CSA) and pregnancy-specific beta-1-glycoprotein (SP1) was seen in every case. Clear positive labelling for placental alkaline phosphatase (PLAP) and human chorionic gonadotropin (HCG) was seen in two cases. Extracellular labelling was found in areas of cell debris, free lying or in phagocytic cells and on tumour cell brush borders. The pattern of intracellular labelling, however, was different for each antigen and reflected the probable sites of synthesis and release from the cells. Thus CEA, a complex glycoprotein, was localised within the golgi apparatus, small apical cytoplasmic vesicles and mucous droplets in relatively well differentiated tumour cells. CSA, a chemically related glycoprotein, had a similar, but less dense distribution. SP1, by contrast, was localised within basally-located vesicles associated with the ribosomal endoplasmic reticulum and appeared to be released and persist as debris or taken up by phagocytic cells below the basal lamina. PLAP and HCG, both proteins, were found within simple single membrane-bound vesicles within relatively undifferentiated cells.

Adenocarcinoma↗
PubMed1985

Ploidy studies in adenomatous polyps of the colon.

The nuclei of colonic adenomatous polyps and some colonic carcinomas have a normal diploid profile. The remaining carcinomas are aneuploid, and this change most probably occurs after the dysplasia that determines invasiveness, because even adenomatous polyps with carcinoma in situ are diploid.

Adenocarcinoma↗
PubMed1985

Gastrointestinal lymphoma.

The gastrointestinal tract is the commonest site for primary extranodal malignant lymphoma. Despite this, gastrointestinal lymphomas are rare and present diagnostic and conceptual challenges. Principal among these are the differential diagnoses of malignant lymphoma and carcinoma and malignant lymphoma and pseudolymphoma, especially in the stomach; the nature of Mediterranean lymphoma and of the lymphoma complicating celiac disease; and the conceptual basis for differentiation of follicular centre cell lymphomas in the intestine.

Adolescent↗
PubMed1984

Abscess induction in beige (bg/bg) mutant mice.

Humans with Chediak-Higashi Syndrome (CHS) and several animal species with similar defects have been reported to have increased susceptibility to infection, including abscess formation, associated with granulocyte abnormalities. These defects were investigated by comparing mice of the SB/Le strain, homozygous for the beige mutation, with their heterozygous littermates and with normal BALB/c mice with respect to the ability to form intraabdominal abscesses. Mice were autopsied 7 days after the intraperitoneal inoculation of a mixture of Bacteroides fragilis, Escherichia coli and an abscess-potentiating agent, bran. Although homozygous beige mice formed more numerous abscesses than controls, the total abscess sizes and bacterial contents were not significantly different. Histopathologically, the abscesses resembled those in normal mice. Phagocytic killing assays using granulocytes from beige mice of the SB/Le and C57BL/6J strains showed no significant differences between homozygous beige mice and controls. Within the context of these experiments in which neutrophil function in vivo and in vitro was examined with respect to anaerobic and facultative Gram-negative bacteria, it is concluded that beige mice can respond adequately to an infectious bacterial challenge. The increased susceptibility to an infection seen in various species with CHS-like disease may relate to virulence factors of the infecting organisms and defects in host defences documented by others but not manifest in these experiments.

Abscess↗
PubMed1983

The cellular response to human colonic neoplasms: macrophage numbers.

Tumour cells and macrophages are thought to interact and the behaviour of tumours may be modified by macrophage activity. Using an immuno-histochemical method for the demonstration of lysozyme and a computerised image analysis system, the number of macrophages was assessed in and around tubulovillous adenomas and the different Dukes grades of adenocarcinomas of the colon. No significant differences were demonstrated and it is concluded that the behaviour of these neoplasms is not related to the number of associated macrophages.

Adenocarcinoma↗
PubMed1983

Tumour marker acquisition in the polyp-to-cancer sequence in the colon.

Sequential studies of 6 tumour markers in an adenomatous polyp which eventually metastesized as adenocarcinoma are described. The findings suggest that with the development of malignancy, clones of cells with an increasing number of markers are favoured for continued growth and that this probably represents progressive gene derepression.

Adenocarcinoma↗