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Biomedical subjects

F T Bosman

Publications and source records attributed to F T Bosman.

265 records · Page 15Linked to original sources

Sézary's syndrome: a cytogenetic, cytophotometric and autoradiographic study.

Cytophotometric, cytogenetic, and autoradiographic studies were performed in cells of three patients suffering from clinically diagnosed Sézary's syndrome with erythroderma and the presence of abnormal lymphoid cells in the peripheral blood, skin, bone marrow and lymph-nodes. Feulgen DNA cytophotometry of cells in the peripheral blood and skin lesions showed marked aneuploidy and tetraploidy. Multiple translocations were identified with a G-banding technique. The chromosomal abnormalities varied widely between the patients, but C and D group chromosomes were more frequently involved than others. All breakpoints of the translocations were localised in the centromeric region. Autoradiography of blood and skin samples revealed many labelled cells in the skin and a lower number in the blood, indicating cell proliferation in the skin. It is concluded that the pathological cells occurring in the Sézary syndrome are abnormal lymphoid cells with a tendency to proliferate in the dermis. The variability observed between and in the patients is in all probability due to a difference in the degree of dedifferentiation.

Aged↗

Type-specific immunodetection of human heart fatty acid-binding protein with polyclonal anti-peptide antibodies.

In order to develop specific antibodies against human heart cytoplasmic fatty acid-binding protein (H-FABPc), four oligo-peptides of 15-20 amino-acids each and corresponding with different antigenic parts of the human H-FABPc molecule, were synthesized. Polyclonal antibodies against these synthetic peptides were raised in mice (Balb/C) and rabbits (Flemish giant). When tested in enzyme linked immunosorbent assays (ELISA, antibody-capture assay), antisera against three of the four peptides showed a high immunoreactivity with the synthetic peptide selected for immunization as well as with the native human H-FABPc. Some cross-reactivity with the other synthetic peptides was observed for the rabbit antisera but not for those from mice. Polyclonal antibodies against synthetic peptides can be applied for the specific detection of the native protein in biological preparations containing proteins that show a high degree of homology with the protein to be assayed.

Amino Acid Sequence↗

Prognostic value of pathological characteristics of colorectal cancer.

The overall cure rate of colon cancer has not improved dramatically in the last decade, remaining at approximately 60% 5-year survival. The main reason for this lack of progress is that at the moment the primary tumour is resected, a significant proportion of the patients with seemingly localised disease already has (undetectable) micrometastases, mostly in the liver. The most important prognostic indicators have been extension of the tumour into the bowel wall and the presence of lymph node metastasis, as expressed in the Dukes classification. However, in the Dukes B and C categories, these parameters are poor predictors of final outcome. For improvement of the prognosis, in addition to earlier detection, more aggressive (adjuvant) treatment of high risk patients would be a rational strategy. This requires development of new therapeutic modalities, but also reliable stratification of patients according to high risk or low risk for recurrent disease. In recent years, many attempts have been made to improve the prediction of final outcome. Parameters studied include inflammatory response to the primary tumour, tumour cell growth fraction, tumour cell differentiation, genetic abnormalities and expression of genes involved in invasion and metastasis. Although some of these newer parameters have significant predictive value, in multivariant analyses, most appear to have limited independent value. Recent studies indicate that genetic abnormalities might be important new prognostic indicators. One of the most promising findings in this area is an allelic loss of chromosome 18q, which allows division of Dukes B patients into subgroups with low risk and high risk for recurrent disease.

Cell Differentiation↗

Basement membranes in bronchogenic squamous cell carcinoma: an immunohistochemical and ultrastructural study.

Basement membrane (BM) deposition at the inter-face of tumor cells and stroma was studied in 27 bronchogenic squamous cell carcinomas. Specimens from peripheral and central parts of each tumor were collected. These were frozen, formalin fixed and paraffin embedded or fixed in Karnovsky's fixative, and processed for electron microscopy. With the use of antibodies to type IV collagen and laminin, the BM was visualized by light microscopy with an indirect immunoperoxidase technique. Light microscopic findings were compared to ultrastructural observations. The peripheral parts of the tumors showed continuous BM in a recognizable preexisting alveolar pattern without evidence of invasive growth into the alveolar septa. In contrast, central parts showed highly variable BM deposition ranging from continuous to almost completely absent. Alveolar patterns were not observed in the tumor centers. The stromal compartment of the tumor centers contained many spindle cells with irregular pericellular BM-like material that could be identified ultrastructurally as myofibroblasts. Electron microscopy and immunohistochemistry yielded virtually identical results. It is concluded that invasive growth in bronchogenic squamous cell carcinomas occurs in central parts of the tumor when the tumor periphery shows expansive growth without invasion of alveolar septa. The situation is different in invasive squamous cell carcinomas originating from other organs because of anatomical differences between the lung and solid organs.

Basement Membrane↗

CEA-specificity of CEA-reactive monoclonal antibodies. Immunochemical and immunocytochemical studies.

Four carcinoembryonic antigen (CEA) reactive monoclonal antibodies Parlam 1, 4, 5 and 6 were studied in respect to reactivity with CEA and its cross-reacting antigens (NCA-1, NCA-2, BGP). In immunochemical studies (ELISA and SDS-PAGE followed by immunoblotting) Parlam 4 did not react with these crossreacting antigens, whereas Parlam 1, 5, and 6 demonstrated variable reactivity with these antigens. As expected, by immunocytochemistry Parlam 1, 5, and 6 stained bile canaliculi in the liver (due to crossreactivity with BGP), pneumocytes and splenic tissue (NCA-1) to an extent comparable with the results in biochemical tests. In contrast with the immunochemical observations, however, Parlam 4 showed slight but distinct reactivity with splenic granulocytes (NCA-1) and hepatic bile canaliculi (BGP). Relative epitope specificity of the monoclonal antibodies was tested in blocking experiments. These showed that Parlam 1 and 5 detect the same epitope on CEA as they block each others binding completely. In other combinations monoclonal antibodies block each others binding only partially, indicating that they detect different or partially overlapping epitopes. These results suggest that CEA specific epitopes may partly overlap with epitopes on crossreacting antigens. In this context, we propose that on crossreacting antigens epitopes exist that are structurally similar to epitopes on CEA or that some epitopes on CEA may consist of a spatial configuration which involves CEA specific as well as non-CEA specific structures. The antibody will show the highest affinity towards CEA, as this molecule contains the uniquely matching or complete epitope and lower affinity towards the crossreacting antigen with an imperfectly matching or only partially available epitope.

Animals↗

Colorectal adenomas: clinical and morphological aspects. A review of 166 polyps from 124 Dutch patients.

In a series of 124 consecutive Dutch patients the clinical and morphological features of 166 endoscopically removed colorectal adenomatous polyps were reviewed. The most frequent clinical symptom was manifest blood loss with the stools (51%), but no specific adenoma symptom seemed to exist. Barium enema X-ray examination was done in 108 patients, whereas all patients were colonoscoped. The routinely performed barium examinations detected 71% of the polyps that were found during endoscopy, but not all X-ray examinations were air contrast barium enemas. A good correlation between the localization of the adenomas after both diagnostic modalities was found, indicating that more than 80% were located in the left part of the colon. Nineteen percent of the patients had had a metachronous (pre)neoplastic lesion removed from their large bowel previously, while 40% of the patients had a synchronous polypoid lesion at the moment of polypectomy. Sixty-two percent of the adenomas were tubular, whereas 38% were villous adenomas. There was a strong correlation between size and villous architecture (r = 0.38; p less than 0.001). The epithelial dysplasia was mild in 21%, moderate in 70% and severe in 9% of the adenomas. The degree of dysplasia correlated well with the villous type of mucosal growth (r = 0.24; p less than 0.005). These findings indicate that, 1) there are no colorectal adenoma specific symptoms, 2) to detect colorectal adenomas colonoscopy is the investigation of choice, 3) after the detection of a colorectal adenoma the whole colon should be investigated, 4) colorectal adenoma patients should be kept under surveillance, and 5) determination of the diameter and of the degree of epithelial cell dysplasia may be helpful in assessing the biological behavior of an adenomatous polyp.

Adenoma↗

Adenosine deaminase complexing protein in cancer studies.

ADCP is a dimeric glycoprotein of about 200KD, for which the physiological role is still obscure. This protein occurs mainly in a membrane bound form in various human tissues. In this paper we review the current literature on ADCP in cancer studies. Soluble ADCP was described to be consistently decreased or absent in cancers of lung, liver, kidney and colon. These findings could not be confirmed by immunohistochemical and quantitative biochemical studies in a series of colorectal-, prostatic-, and renal carcinomas. Only in a third of these tumors a decrease could be demonstrated, whereas in the other cases unaltered or even increased amounts were observed. However, in virally transformed human fibroblasts a consistent decrease or complete absence of ADCP was seen, while primary fibroblasts were found to contain high amounts of this protein. Recently, the use of ADCP as a differentiation marker in colonic cancer has been advocated. Furthermore the presence of ADCP in the serum of renal adenocarcinoma patients was found to be indicative of a better chance of five year survival. These studies suggest that ADCP may be a differentiation marker useful for immunohistochemical characterization of colonic and renal carcinomas as well as a serum marker useful for follow-up studies of these types of cancer, analogous to CEA. Finally, ADCP has been found to be selectively expressed by certain T-cell subsets and henceforth may be useful in the studies on leukemias.

Carrier Proteins↗

Culturing and xenografting of primary colorectal carcinoma cells: comparison of in vitro, and in vivo model and primary tumor.

In a series of 61 primary colorectal carcinomas, we attempted to determine which primary tumor characteristics correlated with the possibility to continuously maintain tumor cells in vitro or in vivo, and to what extent the characteristics of a primary tumor were maintained in vitro or as xenograft. Four continuous cell lines and 10 serially transplantable tumors were obtained. Only one cell line could be maintained both in vitro and in vivo. Tumors that had metastized and tumors in the proximal colon showed a higher success for in vivo and in vitro growth. DNA analysis showed that in most xenografts the DNA index was identical to that the primary tumor. However, in some cases tumor cell subpopulations were lost or genetically variant new subpopulations were generated. In general, the degree of differentiation in the xenografts corresponded with the least differentiated areas in the primary tumor. Xenografts appeared to display comparable of antigen expression.

Animals↗

Abnormal expression of secretory component in term newborns with bowel perforation--a report of two cases.

Expression of secretory component (SC) in intestinal resection specimens from two term newborns with bowel perforation due to necrotizing enterocolitis (NEC) or and NEC-like syndrome was determined and compared with the SC immunoreactivity in a panel of intestinal tissues from fetuses at different ages of gestation. Expression of SC was absent in one patient, whereas in the other patient, SC immunoreactivity was observed in the basal cell part of colonic epithelium only. SC was normally expressed in a follow-up biopsy on one of these patients. In contrast, SC was present in the apical plasma membrane and brush border of colonic epithelium from 32 weeks of gestation onwards in fetuses without demonstrable intestinal disease. From these findings we conclude that the expression of SC was impaired in our patients, thus possibly playing a role in the development of the bowel perforation in these full-term newborns with an NEC-like syndrome or resulting from its pathogenesis.

Enterocolitis, Pseudomembranous↗

Expression of cytokeratin 8 in basal cell carcinoma: a comparative immunohistochemical and immunoelectron microscopy study.

The comparative study reported here was undertaken in order to resolve the discrepancies in the detection of cytokeratin (Ck) 8 reported in previous studies. The expression of Ck 8 was compared in 6 basal cell carcinomas (BCCs) using immunohistochemical and immunoelectron microscopic techniques and a panel of 4 different commercially available monoclonal antibodies (MoAbs). The results of this comparative study demonstrated not only that the consistent expression of Ck 8 using one of the MoAbs in immunohistochemistry was confirmed by immunoelectron microscopy, but that the inconsistent expression of Ck 8 observed using two other MoAbs was also confirmed. One of the MoAbs did not show any staining at all. The inability of this MoAb to detect the expression of Ck 8 using either of the techniques also indicated that this MoAb may be directed against an epitope of Ck8 that is not detectable in BCC in situ.

Aged↗

Tumorigenic behaviour of c-Ha-ras oncogene transfected CaCo 2 cells is associated with increased proteolytic potency.

BACKGROUND: Point mutations within the family of the ras genes are detected in approximately 50% of human colorectal adenomas and carcinomas. Therefore, it is generally accepted that the occurrence of ras-point mutations constitute an important step in colorectal carcinogenesis. In addition, many studies have demonstrated that the tumorigenicity of the human colorectal carcinoma cell line, CaCo 2, strongly increases after transfection with the c-Ha-ras oncogene. This cell line is suitable for gaining more insight into the mechanism of c-Ha-ras induced tumorigenesis. MATERIAL AND METHODS: Proliferation, differentiation, and proteolytic capacity of c-Ha-ras oncogene transfected CaCo 2 cells were studied in vitro. RESULTS: It was found that gelatinolytic capacity and production of urokinasetype plasminogen activator increased, whereas the production of tissue-type plasminogen activator was similar. Proliferative activity, as measured by the potential doubling time, did not alter. The expression of the differentiation markers sucraseiso-maltase, mucin, and chromogranin A was not different from that of the parental CaCo 2 cell line, which indicates that an increased tumorigenic capacity of c Ha-ras oncogene transfected CaCo 2 cells is not accompanied by loss of differentiation. CONCLUSION: These data demonstrate that the highly increased tumorigenic capacity of c Ha-ras oncogene-transfected CaCo 2 cells is associated with an enchanced proteolytic capacity.

Caco-2 Cells↗