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Biomedical subjects

F T Bosman

Publications and source records attributed to F T Bosman.

At least 235 records · Page 13Linked to original sources

Immunohistochemical demonstration of the cytoplasmic copper-associated protein in the liver in primary biliary cirrhosis: its identification as metallothionein.

Metallothionein was isolated from the liver of rats pretreated with cadmium. Monospecific anti-metallothionein antibodies were produced in rabbits. Twenty-six primary biliary cirrhosis (PBC) liver samples and three control liver samples were stained for metallothionein by an indirect immunoperoxidase technique. Nineteen of the PBC samples and the control samples were also stained for copper by Timm's silver sulphide method. In all PBC samples the copper concentration was determined. In addition, the zinc, cadmium, and mercury concentrations were measured in some samples. Eighteen of the PBC samples stained for metallothionein showed marked diffuse cytoplasmic and nuclear staining of a varying number of periportal hepatocytes. In none of them was granular staining detected. None of the control samples showed staining. Fourteen of the PBC samples stained for copper showed diffuse cytoplasmic and granular staining of the periportal hepatocytes. In none of them was nuclear staining detected. None of the control samples showed staining. No elevated zinc, cadmium, or mercury concentrations were found but the copper concentration was increased in 21 of the 26 PBC samples. The number of cells staining for copper and metallothionein was assessed semiquantitatively. Significant correlations were found between the grade of metallothionein staining and the liver copper concentration; the grade of Timm's staining and the liver copper concentration; and the grades of metallothionein staining and Timm's staining. The data suggest that the accumulation of copper induces synthesis of cytoplasmic and nuclear metallothionein, and that the increased amount of cytoplasmic copper is bound to a similarly increased amount of metallothionein.

Adult↗

Amine and peptide hormone production by lung carcinoid: a clinicopathological and immunocytochemical study.

A consecutive series of 38 lung carcinoid tumours (36 surgical and two necropsy specimens) was studied. Histopathological features and amine and peptide hormone immunoreactivity were correlated with gross characteristics (size, location) and clinical data. Peripheral carcinoids were detected a decade later than central carcinoids and tended to be bigger. In general, the histological characteristics of peripheral and central carcinoids were similar; atypical features, however, were more common in peripheral carcinoids. Most carcinoids contained many argyrophilic cells (58%). Although argentaffinic cells were not found, serotonin immunoreactive cells were present in 32% of the tumours. Peptide hormone immunoreactivity (adrenocorticotrophic hormone (ACTH), calcitonin, somatostatin, gastrin) was rare. In one case massive ACTH production had caused clinically manifest Cushing's syndrome. In two other cases few ACTH immunoreactive cells were found and in one case calcitonin immunoreactive cells were present. The relative rarity of hormone production in lung carcinoids and the predominantly benign course of the tumour preclude the use of peptide hormone production as a prognostic indicator.

Adolescent↗

Growth hormone releasing factor (GRF) immunoreactivity in human and rat gastrointestinal tract and pancreas.

Rabbit antisera were raised against a synthetic growth hormone releasing factor, which was originally isolated from a human pancreatic endocrine tumor (hpGRF-44). The antisera obtained showed no significant cross-reactivity with a variety of neurohormonal peptides. In addition to its occurrence in the human, but not in the rat, hypothalamus, hpGRF-44-like immunoreactivity was identified in human gastric antrum and human as well as rat pancreatic islets, using an indirect immunoperoxidase technique. Staining of serial sections and double staining revealed that in the gastric antrum the immunoreactivity was largely confined to gastrin (G) cells, whereas in pancreatic islets polypeptide (pp) cells were reactive. The physiological significance of these findings remains to be established.

Animals↗

Quantitative changes in adenosine deaminase isoenzymes in human colorectal adenocarcinomas.

Several reports have suggested that a decrease or absence of adenosine deaminase complexing protein (ADCP) is consistently associated with cancer. However, in other studies, decreased as well as increased ADCP levels were found. In the present study, we investigated ADCP levels in 37 colorectal adenocarcinomas and correlated the results with clinicopathological characteristics in individual carcinomas. The levels of adenosine deaminase (EC 3.5.4.4) and soluble ADCP were determined in tissue samples by, respectively, a spectrophotometric assay and an ADCP specific radioimmunoassay. The values in the individual tumors were compared with their histological characteristics, such as degree of differentiation, nuclear grading, and the preoperative plasma carcinoembryonic antigen levels in the patients. It was found that ADCP was decreased in about a third of the tumors but unaltered or even increased in others. However, there was an overall 40% increase of the adenosine deaminase activity in the tumors compared to normal tissue. There seems to be no simple correlation between any of the clinicopathological parameters and the ADCP or adenosine deaminase levels. Methods detecting ADCP at single cell level might be helpful in exploring its potential use as a cancer-associated marker.

Adenocarcinoma↗

Monoclonal antibody (1116 NS 19-9) defined monosialoganglioside (GICA) in colorectal carcinoma in relation to stage, histopathology and DNA flow cytometry.

Immunoreactivity of 1116 NS 19-9 monoclonal antibody defined monosialoganglioside (gastrointestinal cancer-associated antigen, GICA) has been studied in a series of colorectal carcinoma patients of a multicentre prospective controlled trial in order to assess its correlation with parameters such as localization, stage histopathological characteristics and DNA flow cytometry. GICA could be detected in 60% of the carcinomas, but no correlation was observed between its status of immunoreactivity and any of the parameters studied. It is concluded that, though study of the expression of the monosialganglioside may be worth while in relation to fundamental aspects of behaviour of colorectal carcinomas, the significance of its immunohistochemical detection in a diagnostic or prognostic sense is limited.

Antibodies, Monoclonal↗

Efficiency and sensitivity of indirect immunoperoxidase methods.

The peroxidase-antiperoxidase (PAP) complex method has repeatedly been claimed to be more sensitive and antibody efficient than the indirect peroxidase labeled antibody method. However, most studies comparing these methods used tissue sections as the test material. However, test systems with known amounts of antigen will allow more reliable comparison of these methods and quantitative evaluation of method sensitivity. We therefore compared the antibody efficiency and sensitivity of these methods for the detection of human chorionic gonadotropin in an enzyme linked immunosorbent assay (ELISA), an antigen spot test (AST) and tissue sections of choriocarcinoma. In the PAP technique rabbit PAP and goat anti-rabbit antibody were applied. The same antibody was peroxidase-labeled with the periodate technique and used in the labeled antibody method. In the ELISA the PAP method resulted in slightly higher antibody efficiency than the labeled antibody method. At low primary antibody dilutions the intensity of the reaction decreased with the PAP method but remained high with the labeled antibody method, in the ELISA as well as on tissue sections. In the AST the labeled antibody method and the PAP method appeared to be equally sensitive.

Antigen-Antibody Reactions↗

Undifferentiated carcinoma of the colon containing exocrine, neuroendocrine and squamous cells.

The light microscopic, electron microscopic and histochemical features of a highly malignant colonic tumor resected from a 39 year old man are presented. The tumor was composed predominantly of undifferentiated cells with focally admixed neuroendocrine, exocrine and squamous cells, occasionally arranged in an organoid manner. Histochemically the tumor contained argyrophilic cells as well as cells that reacted positively with the antibodies to alpha-1-antitrypsin, alpha-1-antichymotrypsin, carcinoembryonic antigen and lysozyme. The term "stem cell carcinoma of the intestine" is proposed for this highly malignant tumor composed of undifferentiated cells exhibiting only focally their multidirectional developmental capacity.

Adult↗

Some recent developments in immunocytochemistry.

Immunocytochemistry has become an indispensable tool both in basic biomedical research and in diagnostic histopathology. Several recent innovations have led to improvements in the sensitivity; specificity and precision of these techniques. Numerous modifications of the original methods have been developed, many with increased sensitivity. In particular, methods using protein A or the avidin-biotin complex as second steps appear to be promising. New methods for the quantitative determination of sensitivity have become available. The introduction of monoclonal antibodies as immunocytochemical reagents appears to be a major improvement. New methods of immunochemical analysis, such as immunoblotting and immunospotting of antigens extracted from tissue specimens, allow the molecular composition of immunoreactive antigenic sites in a tissue to be analysed. The accuracy of localization in immunoelectron microscopy has been improved significantly through the use of ultracryotomy of unfixed tissue in combination with colloidal gold particles as a label. In addition, gold particles can be counted and thus allow relatively simple quantification of the immune reaction. Using flow cytometry, especially in combination with monoclonal antibodies, quantitative immunofluorescence has become feasible.

3,3'-Diaminobenzidine↗

Distribution of monoclonal antibody-defined monosialoganglioside in normal and cancerous human tissues: an immunoperoxidase study.

The immunoreactivity of a monosialoganglioside antigen defined by monoclonal antibody 116NS19-9 (19-9) was studied in neoplastic and normal glandular and mucosal epithelia using an indirect immunoperoxidase method. In neoplastic mucosae, the antigen was detected in the majority of colorectal and endometrial carcinomas, predominantly in a focal staining pattern. A substantial proportion of gastric and pancreatic tumors and an occasional breast carcinoma also reacted with the monoclonal antibody. Expression of the monosialoganglioside in normal colonic mucosa appeared to be restricted to areas adjacent to tumor tissue. In gastric mucosa, the antigen was confined to some areas showing intestinal metaplasia. The antigen was also detected in the epithelium of normal mucosa of the gall bladder and endocervix, as well as in some ductal epithelia of the pancreas and salivary glands. Most other mucosae were negative for antigen expression.

Adenocarcinoma↗

Immunohistochemical study of the distribution of secretory component and IgA in the normal and diseased uterine mucosa.

The distribution of secretory component (SC) and IgA in the normal and diseased uterine mucosa was studied by means of an immunoperoxidase method. Both substances could not be demonstrated in ectocervical epithelium, whereas in endocervical epithelium both were present and staining intensity appeared to be related to the degree of inflammatory activity in the underlying stroma. Local IgA-containing plasma cells most likely are the source of epithelial IgA. Well-differentiated adenocarcinomas of the endocervix were shown to display SC immunoreactivity. In endometrial glands SC was observed in the postovulatory phase of the menstrual cycle, in increasing quantities toward menstruation. Hyperplastic conditions of the endometrium showed a weak focal staining for SC. In contrast, in most well-differentiated adenocarcinomas of the endometrium, SC and IgA could be detected in most neoplastic elements, whereas poorly differentiated carcinomas were largely negative. It is concluded that: (a) in contrast to the endometrium, in the endocervix a local secretory immune system operates similar to that of the gastrointestinal tract; (b) the ability of the endometrium to synthesize SC is at least partly regulated by hormonal factors and, as such, is confined to the progestagen-dominated phase of the menstrual cycle; and (c) immunohistochemical detection of SC may be of help in the grading of adenocarcinomas of the endometrium.

Adenocarcinoma↗

Neuroendocrine cells in cystic mucinous tumours of the ovary.

This histogenesis of cystic mucinous ovarian tumours is still controversial. It has been proposed that these neoplasms may arise from metaplastic ovarian surface epithelium. Others have suggested that these tumours represent monophyletic (intestinal) types of teratoma. Against this background we have studied the presence of different types of neuroendocrine cells in a series of cystic mucinous ovarian tumours. Argyrophil neuroendocrine cells were found almost exclusively in tumours which were histologically classified as borderline or low-grade mucinous carcinomas, whereas these cells were very rare in mucinous cystadenomas and in grade III and IV carcinomas. Several gut peptide hormones could be demonstrated in these cells, but only in borderline tumours and low-grade mucinous carcinomas. Mucin histochemistry did not reveal characteristic patterns in these neoplasms. The results confirm that with regard to the presence of endocrine cells the epithelium of borderline mucinous cystadenomas and mucinous cystadenocarcinomas bears strong resemblance to intestinal epithelium. These findings do not rule out the possibility that these tumours arise by metaplasia from ovarian germinal epithelium but are equally compatible with a teratomatous origin. The epithelium of most benign mucinous cystadenomas resembles that of ovarian inclusion cysts.

Chromaffin System↗

Immunohistological findings in lip biopsy specimens from patients with Crohn's disease and healthy subjects.

Biopsies of apparently normal buccal mucosa were taken from 14 patients with Crohn's disease and 13 healthy controls who were matched for dental status. Most patients had an increased number of lymphocytes around vessels in the subepithelial tissue and two showed fibrosis with moderate atrophy of minor glands. Plasma cells which contained immunoglobulin, predominantly IgA, were only found around minor salivary glands in both patients and controls. Quantitative studies showed a significant increase in the number of cells containing IgA in patients compared with controls. No correlation was found between immunoglobulin pattern and disease activity, age, sex, or duration of Crohn's disease. A significant correlation was found between the activity of the disease, as defined by the Crohn's Disease Activity Index, and the number of plasma cells containing IgM.

Adult↗

Immunoelectronmicroscopy of metaphase chromosomes.

A method for the preparation of ultrathin sections of metaphase chromosomes is described. This method was applied to human metaphase chromosomes, which were immunocytochemically stained with anti-DNA and anti-ribonucleoprotein antibodies, derived from patients with auto-immune disease. Conventionally prepared metaphase spreads as well as cytocentrifuge preparations of chromosome suspensions were studied. The results indicate that the ultrastructure of chromosomes and the immunoreactivity of chromosomal constituents are influenced by the applied preparation methods. In comparison with whole mount preparations, ultrathin sections of immunostained chromosomes allow higher resolution and more precise localization of immunoreactive sites within the chromosomal structure.

Antibodies, Antinuclear↗

Medullary differentiation of anaplastic thyroid carcinoma.

Fourteen cases of anaplastic carcinoma of the thyroid (ACT) were studied with silver staining and immunohistochemical technics for signs of medullary differentiation. For comparison a series of 11 cases of medullary carcinoma of the thyroid (MCT) was studied. In nine out of 14 cases of ACT both argyrophilia and immunoreactive calcitonin could be detected as evidence of an apparent C-cel origin of these tumors. Most of the patients with these anaplastic medullary carcinomas died within 6 months after the histological diagnosis was made. It is concluded that the histological diagnosis of anaplastic variants of MCT can only be made on the basis of argyrophilic cytoplasmic granules and calcitonin immunoreactivity. In contrast to well differentiated MCT the anaplastic medullary carcinoma is characterized by a poor prognosis.

Adrenocorticotropic Hormone↗

Polyethylene glycol embedded tissue sections for immunoelectronmicroscopy.

Several methods for tissue embedding in polyethylene glycol (PEG) were compared with regard to their applicability for pre-embedding immunoelectronmicroscopy. Existing embedding procedures gave unsatisfactory results and therefore a modified procedure was developed. This method, consisting of very brief tissue infiltration with PEG 1500, to which 3% water is added, allowed adequate tissue sectioning. Using these sections for preembedding immunoelectronmicroscopical localisation of glucagon in bovine pancreatic islets adequate ultrastructural morphology was obtained in combination with excellent preservation of peptide hormone immunoreactivity.

Animals↗