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Biomedical subjects

E Kaiserling

Publications and source records attributed to E Kaiserling.

At least 73 records · Page 4Linked to original sources

A CD44 variant exon 6 epitope as a prognostic indicator in breast cancer.

The CD44 variant exon 6 sequence is associated with metastasizing clones of rat pancreatic and mammary carcinoma. In human breast and colorectal carcinoma epitopes on the cell surface encoded by exon v6 have been shown to predict poor chances of survival. Breast cancers in 55 patients whose clinical follow-up was available for 6 to 8 years were immunophenotyped for the presence of the CD44 exon v6 epitope and the results were correlated with survival. There was a difference in survival in the first 2.5 years following surgery: of the eight patients with negative tumours none had died during this period. The advantage of the negative group faded at later time points. However, the log-rank analysis revealed that differences between CD44 exon v6-negative and -positive groups were just below statistical significance. Studies with a larger number of patients are needed to establish the role of this CD44 variant as an early prognostic indicator in metastatic dissemination of breast cancer.

Antigens, Neoplasm↗

Lipid islands in human gastric mucosa: morphological and immunohistochemical findings.

BACKGROUND & AIMS: Lipid islands are a common finding in the gastric mucosa, but their pathogenesis has not yet been established. The aim of this study was to investigate the morphology and immunophenotype of the various cells in lipid islands and to consider the possible mechanisms involved in the pathogenesis of these lesions. METHODS: Morphological and immunohistochemical investigations using antibodies against macrophages, smooth muscle cells, and lymphocytes were performed. Unfixed tissue was available for immunostaining for low-density lipoprotein (LDL) and oxidized LDL in one case. RESULTS: The lipid islands were composed of KP1-, KiM1p-, and cathepsin D-positive foam cells that were only weakly reactive for lysozyme. In cryostat sections, the foam cells were found to contain LDL and oxidized LDL. A few smooth muscle cells, plasma cells, lymphocytes, pericytes, fibroblasts, and Schwann cells that contained lipid droplets were also found. CONCLUSIONS: In gastric lipid islands, the presence of oxidized LDL, which is taken up by macrophages and smooth muscle cells via scavenger receptors, suggests that oxidized LDL is of key significance in the development and persistence of these lesions. Because the metabolism of LDL to oxidized LDL may occur by various mechanisms, various different initial conditions, including gastritis, may precede the development of lipid islands. Thus, anti-inflammatory treatment may be appropriate.

Foam Cells↗

A comparison of methods for heat-mediated antigen retrieval for immunoelectron microscopy: demonstration of cytokeratin No. 18 in normal and neoplastic hepatocytes.

Postembedding antigen retrieval is a well established technique for immunoelectron microscopy; however, many antigens cannot be detected without additional unmasking procedures. This study was undertaken to determine whether microwave oven heating, autoclaving, and pressurized boiling, which are well recognized methods of antigen retrieval for light microscopy, and simple boiling can also be used in electron microscopy. We investigated neoplastic and normal hepatocytes using a commercially available mouse monoclonal antibody against cytokeratin NO. 18 (CK 18). The tissue was fixed in paraformaldehyde/glutaraldehyde and embedded in Lowicryl K4M at -40 C. Ultrathin sections in various buffers were exposed to heat using one of four methods or to pronase at 37 C before incubation with the primary antibody. The secondary antibody was gold-labeled goat anti-mouse antibody. Sections that were not heat-treated remained unlabeled, but heat-treated sections showed immunoreactivity located mainly at the cytoplasmic periphery. Some of the gold particles lay in direct or loose association with intermediate filaments, some were seen in the area of desmosomes, and some did not appear related to any structures. No difference in immunostaining was found among the four methods of heat treatment. The citrate buffer, pH 6.0, and 10 mM EDTA, pH 8.0, generated the best labeling results.

Antigens↗

Small epithelial cells and the histogenesis of hepatoblastoma. Electron microscopic, immunoelectron microscopic, and immunohistochemical findings.

The wide range of epithelial and mesenchymal lines of differentiation seen in hepatoblastoma suggests that this tumor derives from a pluripotent stem cell. To test this hypothesis, seven hepatoblastomas of various subtypes were investigated for the presence of cells with the features of the oval cells found during hepatocarcinogenesis in rodents that are thought to be closely related to hepatic stem cells. Because similar cells, referred to as "small cells," have been described in human liver disease with chronic ductular reaction, five liver biopsies from infants with biliary atresia were also investigated. The specimens were investigated by electron microscopy, immunoelectron microscopy, and immunostaining for cytokeratins 7, 8, 18, and 19. Small epithelial cells (SEC) corresponding to the oval cells of the rat and the "small cells" in humans were found in both biliary atresia and hepatoblastoma. These cells were oval and exhibited intercellular junctions, tonofilament bundles, and a biliary epithelium-type cytokeratin profile. SEC were found in small numbers in fetal hepatoblastoma and in moderate numbers in embryonal hepatoblastoma. In small cell hepatoblastoma, nearly all the tumor cells exhibited SEC-like ultrastructural features and a corresponding cytokeratin profile. Thus, cells exhibiting morphological and immunophenotypic features of hepatic stem cells are detectable in hepatoblastoma. Their numbers vary according to the subtype, reflecting the differing degrees of differentiation of the various subtypes, consistent with the theory propounded in the literature that embryonal and, with further differentiation, fetal tumor cells derive from precursor small cells. The findings support the hypothesis that hepatoblastoma derives from a pluripotent, probably entodermal or even less committed, stem cell.

Biliary Atresia↗

Immunohistochemical and cytogenetic findings in malignant rhabdoid tumor.

BACKGROUND: The histogenesis of malignant rhabdoid tumor (RT) remains a matter of controversy. From published reports it appears that some extrarenal RT (ERRT) exhibit neural or neuroectodermal features. Systematic investigation of renal RT (RRT) for neural differentiation has not yet been published. In this study, two RRT and two ERRT were investigated by light and electron microscopy, immunocytochemistry, and cytogenetic analysis. RESULTS: All four cases exhibited similar morphology and a largely consistent immunohistochemical staining profile. Both tumor types showed immunoreactivity for various cytokeratins, epithelial membrane antigen (EMA), vimentin, neurofilaments, S100 protein, neuron specific enolase, Leu7, CD34, p53, MB2, MIC2, VS38c, laminin and fibronectin. Reactivity was usually confined to a small proportion of the tumor cells, especially in the case of antibodies against neurofilaments, NSE, S100 proteins Leu7, CD34 and p53. Only a few of the antibodies (anti-vimentin, MB2, MIC2, anti-EMA, and VS38c) stained the majority of the tumor cells. Chromosome analysis revealed a discrete aberration in 11p (most probably a paracentric inversion in 11p15) in the one RRT investigated. One ERRT had a normal karyotype, but the other one exhibited various structural abnormalities on chromosomes 18 and 22. CONCLUSIONS: The immunohistochemical investigations revealed many similarities between RRT and ERRT, and all four tumors investigated exhibited neuroectodermal differentiation. As far as histogenetic classification is concerned, our findings point in the direction of the group of tumors that includes Ewing's sarcoma and primitive neuroectodermal tumors.

Cytogenetics↗

[Primary plasmacytoma of the lymph node (plasmocytic lymphoma). The differential diagnosis of nodal plasma-cell proliferates].

HISTORY AND CLINICAL FINDINGS: A 60-year-old man was found on routine examination to have an enlarged, firm, cervical lymph node. He looked older than his age and his general condition was poor. He had no fever, nocturnal sweating or weight loss. Further examination revealed no hepatosplenomegaly on palpation, but numerous enlarged cervical lymph nodes were palpable. INVESTIGATIONS: Histological investigation of a cervical lymph node revealed a marked increase in slightly pleomorphic plasma cells with monotypic expression of IgM-kappa. Multiple myeloma was excluded on the basis of histological and cytological findings in the bone marrow. Serology revealed a mild antibody deficiency syndrome (gamma-globulin 7.8%) with signs of acute inflammation and an increase in alpha 2-globulin. There was no evidence of a monoclonal gammopathy on electrophoresis. A diagnosis of primary nodal plasmacytoma was made. COURSE: As the patient was asymptomatic at diagnosis he was not given chemotherapy. There was no evidence of tumour progression at follow-up examination two months later. His progress will be monitored closely. CONCLUSION: This patient's history is consistent with the prognosis generally associated with primary nodal plasmacytoma that is much better than that of multiple myeloma.

Diagnosis, Differential↗

Expression of the p53 tumour suppressor gene in human placenta: an immunohistochemical study.

Since human trophoblast undergoes extensive proliferation and exhibits invasive growth comparable to that of a malignant tumour, human placenta at various different stages of gestation was investigated immunohistochemically with the monoclonal antibody Ab-6 for expression of the p53 tumour suppressor gene. p53 protein was detected in the nuclei of a few trophoblastic cells, almost all belonging to the cytotrophoblast and only very few to the syncytiotrophoblast, in nearly all specimens investigated (first trimester 10/10, second trimester 5/5, third trimester 4/5). First trimester trophoblast exhibited increased expression of p53 protein in the juxtastromal areas of cytotrophoblast cell islands and columns, that is, in areas where high proliferative activity and increased expression of the epidermal growth factor receptor have been described in the literature. Staining was also occasionally seen in trophoblast invading the myometrium. It is most likely that immunohistochemically detectable expression of p53 protein in the trophoblast is due not to mutation of the gene, as in malignant tumours, but rather to up-regulation of the p53 tumour suppressor gene, which could be a mechanism for controlling trophoblast proliferation.

Antibodies, Monoclonal↗

Involvement of the larynx by hemopoietic neoplasms. An investigation of autopsy cases and review of the literature.

Involvement of the larynx by hemopoietic tumors is generally considered a rare event and little is known about the associated clinicopathologic features. Laryngeal tissue removed at autopsy from 14 patients with known disseminated hematologic malignancies and at operation from one patient with multicentric malignant lymphoma of low-grade malignancy (MALToma) of the head and neck region was investigated. A systematic survey of the main clinicopathologic features of the published cases of hemopoietic tumors with laryngeal involvement was also performed. Primary involvement of the larynx by hemopoietic neoplasms must be clearly distinguished from secondary involvement by disseminated or leukemic tumors. Most of the primary tumors are localized lesions that may involve the regional lymph nodes (stages IE or IIE). Radiotherapy is the treatment of choice, and the prognosis is generally favorable. However, secondary involvement by disseminated or leukemic disease carries a very poor prognosis in most cases. Extramedullary plasmacytoma and non-Hodgkin's lymphoma (NHL), particularly B-cell lymphoma of high-grade malignancy, appear to be the most common hemopoietic tumors with primary laryngeal involvement, while primary tumors of myelogenous origin (granulocytic sarcoma and mast cell sarcoma) are extremely rare. Extramedullary plasmacytoma and NHL occur mainly in older persons and in men, are generally associated with a relatively short history of hoarseness and dysphagia, and exhibit preferential involvement of the supraglottic parts of the larynx, in particular the epiglottis and aryepiglottic folds. They are generally polypoid, non-ulcerated lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

Congenital epulis and granular cell tumor: a histologic and immunohistochemical study.

OBJECTIVES: Although it is now reasonably certain that granular cell tumors derive from Schwann cells, the histogenesis of congenital epulis, which is largely isomorphic with granular cell tumor, remains unclear. A study was undertaken to compare the immunophenotype of these tumors with particular emphasis on the expression of matrix proteins and macrophage markers because such information is not available in the literature. STUDY DESIGN: Four granular cell tumors and two congenital epulis were immunostained with a panel of 29 antibodies. Two congenital epulis and one granular cell tumor were investigated by electron microscopy, the latter also by immunoelectron microscopy. RESULTS: Many similarities in immunostaining were found, for example, both tumor types were CD68+, Ki-M1P+, lysozyme-, vimentin+, fibronectin+, laminin+, lectin PHAE+, and lectin WGA+. However, differences were also noted, for example, granular cell tumor was always S100 protein+, but only one congenital epulis case was reactive (weak reactivity after microwave treatment), and staining with the proliferation markers anti-proliferating cell nuclear antigen and MIB 1 was found only in congenital epulis. Both tumor types exhibited pericellular and diffuse cytoplasmic staining for fibronectin and laminin. CONCLUSIONS: The hypothesis that congenital epulis and granular cell tumor would exhibit similar reactivity for macrophage markers was confirmed: both were reactive with anti-CD68 and Ki-M1P and nonreactive with MAC387, anti-lysozyme, and 3A5. Intracytoplasmic staining for fibronectin and laminin, which has not been described previously in these tumors, appears to be a characteristic feature common to both tumors. This finding suggests that there could be a disturbance of synthesis and secretion of extracellular matrix proteins or a derangement of their receptor systems. This theory could be supported by the finding of intracytoplasmic CD49e-positive material in two cases.

Antibodies, Monoclonal↗

Immunoreactivity of sinusoids in hepatoblastoma: an immunohistochemical study using lectin UEA-1 and antibodies against endothelium-associated antigens, including CD34.

Sinusoids are found not only in the normal liver but also in certain liver tumours, including hepatoblastoma, the most common malignant liver tumour in childhood. In this study, sinusoids in 12 hepatoblastomas, of various subtypes, and in normal liver were investigated with UEA-1 and antibodies against von Willebrand's factor, CD31 and CD34 to detect differences of possible diagnostic significance. In the normal liver, staining of sinusoids was seen with all these markers, but it was focal and confined to a few sinusoids near the portal tracts. In hepatoblastoma, the endothelial markers reacted with the sinusoids to varying extents. UEA-1 and anti-CD34 usually stained the majority of these vessels, anti-CD34 staining greater numbers of sinusoids and with greater intensity. Immunostaining revealed that both number and spatial organization of sinusoids in hepatoblastoma are dependent on the subtype. In addition to staining of endothelium, one of the two small cell hepatoblastomas exhibited strong immunoreactivity of the tumour cells for CD34. These findings show that the marked difference in sinusoidal immunoreactivity for CD34 between normal liver and hepatoblastoma could be useful for discriminating between non-neoplastic liver tissue and highly differentiated fetal hepatoblastoma. Our findings also show that small cell hepatoblastoma, in addition to acute leukaemia, should be considered when immunoreactivity for CD34 is found in small round and blue cell tumours in childhood.

Antigens, CD↗

Flow cytometric evaluation of nuclear DNA content in hepatoblastoma: further evidence for the inhomogeneity of the different subtypes.

The DNA ploidy pattern of nine hepatoblastomas and three normal liver specimens was investigated by flow cytometry. Areas of unlike differentiation in the same tumor were investigated separately. Normal liver tissue and the fetal subtype were always diploid. Aneuploidy was found in the embryonal subtype. The one case of small cell tumor was also diploid. When the fetal and embryonal areas of the same tumor were analyzed together, there was always an aneuploid peak in the histogram. There are obvious differences in DNA ploidy among the various hepatoblastoma subtypes. Differences in methods used, including the failure in some studies to evaluate areas of unlike differentiation in the same tumor separately, probably account to some extent for the conflicting results of previously reported studies. When flow cytometric analysis of the DNA content of a hepatoblastoma is performed, it is important to ensure that the various types of differentiation in the tumor are represented adequately in the material investigated, especially when conclusions about the prognosis are to be based on these findings.

Aneuploidy↗

Evidence for a lymphotropic nature of circulating plasmacytoid monocytes: findings from a case of CD56+ chronic myelomonocytic leukemia.

Because the cells previously designated plasmacytoid T cells share major immunophenotypic features with cells of the mononuclear-phagocyte system, they have been re-named and are now known as plasmacytoid monocytes (PM). We describe a unique case of chronic myelomonocytic leukemia with circulating PM. The patient, a 48-year-old man, presented initially with refractory anemia. Four years later his general condition deteriorated, accompanied by an increase in leukocytes to 200,000/microliters blood. The bone marrow histology was interpreted as compatible with a diagnosis of chronic myelomonocytic leukemia. Two months before he died, the patient developed generalized lymphadenopathy clinically simulating malignant lymphoma. Histologic examination of an axillary lymph node revealed diffuse infiltration by PM. The PM in the lymph node and some circulating cells closely resembling PM expressed L-selectin, a finding that could be interpreted as a morphologic correlate of their marked lymphotropism. The detection of large numbers of CD56/CD33 double-positive circulating blast cells by FACS analysis strongly supported the diagnosis of a leukemia of myelogenous origin. The patient died of tumor cachexia. Autopsy revealed widespread leukemic infiltrates (always containing clusters of PM) in bone marrow, spleen, liver, lymph nodes, and mucosa-associated lymphoid tissue of the oropharynx. The final diagnosis was one of chronic myelomonocytic leukemia with marked lymphotropism and partial differentiation towards PM. We consider that the rare instances of a hematologic tumor with differentiation towards PM should be classified amongst the myelogenous leukemias.

Antigens, CD↗

Comparative analysis of the immunophenotypes of decidual and peripheral blood large granular lymphocytes and T cells during early human pregnancy.

PROBLEM: The functional role of the leukocytes in the decidual is not clear. They may regulate the maternal immune response to the fetal allograft. However, the factors controlling maternal and fetal communication have not yet been identified. METHOD: A comparative analysis of the phenotypes of decidual and peripheral blood large granular lymphocytes (LGLs) and T lymphocytes in early human pregnancy was performed on decidual tissue and blood samples obtained from ten patients at therapeutic abortion. RESULTS: Whereas most of the decidual LGLs were found to have a CD56bright++ phenotype, most of the peripheral blood NK cells (90%) showed the classical CD56dim+ phenotype, and only a small proportion were CD56bright+ cells. Another striking difference was found in the expression of very late antigen 1 (VLA-1, CD49a): Almost all the decidual CD56bright++ LGLs, but virtually none of the peripheral blood CD56+ NK cells expressed this antigen. Further differences were found in the expression of CD16, CD44, CD45RA, CD54, and CD57. There were also differences in phenotype between T cells derived from decidual tissue and those derived from peripheral blood. Approximately 31% of the CD3+ decidual T cells expressed VLA-1, but this antigen was virtually absent on peripheral blood T cells. A further difference was seen in the expression of HLA-DR. This activation antigen was found on 32 +/- 13% of the decidual T cells but only 8 +/- 5% of the peripheral blood T cells. Additionally, the proportion of cells expressing CD38 was higher among decidual than peripheral blood T cells. CONCLUSION: The findings suggest that both decidual LGLs and a subset of decidual T cells are activated and possibly play a role in the control of trophoblast growth and placental development.

CD56 Antigen↗