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Biomedical subjects

J Gerdes

Publications and source records attributed to J Gerdes.

At least 145 records · Page 8Linked to original sources

Biochemical characterization and biosynthesis of the Ki-1 antigen in Hodgkin-derived and virus-transformed human B and T lymphoid cell lines.

The Hodgkin-associated Ki-1 antigen was analyzed in different cell lines. In Hodgkin analogous L428 cells, biosynthetically labeled with radioactive amino acids, the Ki-1 antibody precipitated three glycoproteins with 90, 105, and 120 kDa, respectively. Surface-labeling revealed that the two larger components were membrane-associated forms of the Ki-1 antigen, although the 90-kDa molecule was shown in pulse-chase experiments to be the precursor of the 105- and 120-kDa forms. All three forms of the Ki-1 antigen possess a tunicamycin-sensitive 6-kDa N-linked carbohydrate moiety. O-Linked oligosaccharides could not be detected. Thus, the differences in m.w. are probably not due to glycosylation. The ionophore monensin prevented the appearance of the membrane-associated molecules, which demonstrated that they are assembled between the transcompartment of the Golgi complex and their insertion into the cell membrane. The 90-kDa precursor molecule cannot be generated by disulfide reduction from the two larger forms. After internal labeling with P-32, only the 105- and 120-kDa bands became visible, indicating that the Ki-1 molecule is phosphorylated after its processing into the two larger membrane-associated forms. Analysis of the Ki-1 antigens from other cell lines demonstrated that after external labeling of two other Hodgkin-derived cell lines, six Epstein-Barr virus lymphoblastoid cell lines and one human T leukemia virus I-positive T cell line, both the 105- and the 120-kDa membrane molecules could be detected, regardless of the presence or type of virus integrated.

Antigens, Neoplasm↗

The correlation of growth fractions with histologic grading and lymph node status in human mammary carcinoma.

The monoclonal antibody Ki-67 reacts with a human nuclear associated with cell proliferation that is expressed only in the G1, S, G2, and M phases of continuously cycling cells. This offers a simple opportunity to determine the growth fraction of tumors by immunostaining of fresh tissue. One hundred fifty-four invasive carcinomas of the breast were used in this study. The average number of Ki-67 positive cells was 15.3 +/- 10.1% (range, 1%-48%), whereas in 41 benign lesions of the breast only 4.4 +/- 2.6% (range, 1%-10%) of cells were positive. A correlation was found between growth fractions and histologic grading. On average, N+ tumors with less than four positive lymph nodes had a significantly higher growth fraction (20.4 +/- 14.2%) than N0 tumors (13.0 +/- 9.2%), whereas N+ tumors with more than three lymph node metastases had only 17.3 +/- 3.6% Ki-67 positive cells. This method yielded similar results to those obtained by other researchers through the use of flow cytometry and thymidine labeling. Determination of growth fractions by Ki-67 is suitable for routine use and may be useful in prognosis and in the selection of patients for various treatment modalities.

Antibodies, Monoclonal↗

Determination of growth fractions in benign breast disease (BBD) with monoclonal antibody Ki-67.

Certain types of benign breast disease (BBD) carry an increased risk of malignancy. Several morphological criteria such as an atypia score are used to define this group, and the use of a kinetic parameter may provide additional information. Therefore, the growth fractions of 120 benign breast lesions were determined using the monoclonal antibody Ki-67. The values obtained range from 0.3% to 10.8% (average 3.1% +/- 2.2%) compared to breast carcinomas with an average of 15.3% +/- 10.1%, range 0.8% to 47.8%. All specimens were classified using the terminology of Azzopardi. The prevailing histological entities were cystic disease, fibroadenoma, and blunt duct adenosis. Between these groups no differences in growth fractions were observed. Postmenopausal patients had slightly lower values than premenopausal women. Further prospective studies are needed to evaluate whether those cases of BBD with a high number of Ki-67 positive cells have an increased risk of breast cancer, independently from conventional histological classifications.

Adenoma↗

Expression of a Hodgkin and Reed-Sternberg cell associated antigen (Ki-1) in cutaneous lymphoid infiltrates.

Skin biopsy specimens from normal skin and from 115 patients with benign dermatoses, pre- or pseudo-malignant disorders or malignant cutaneous lymphomas have been examined immunohistologically for expression of the Reed-Sternberg cell associated antigen CD30 detected by monoclonal antibodies Ki-1 and Ber-H2. The antibodies stained the atypical cells in lymphomatoid papulosis, a proportion of the neoplastic cells in some cases of mycosis fungoides and most of the neoplastic cells in six large cell anaplastic/pleomorphic non-Hodgkin's lymphomas. The lymphoid cells in all other specimens were Ki-1- and Ber-H2-negative. In all cases, expression of the Ki-1/Ber-H2 antigen was accompanied by expression of activation and proliferation associated markers (i.e., HLA-DR, IL-2 receptor, transferrin receptor and the Ki-67 nuclear antigen). These data indicate the value of antibodies Ki-1 and Ber-H2 in distinguishing between lymphomatoid papulosis and other types of pre- or pseudo-malignant disorders and support the view that lymphomatoid papulosis, Hodgkin's disease and some types of non-Hodgkin's lymphoma constitute a spectrum of related disorders, originated from activated lymphoid cells.

Antibodies, Monoclonal↗

Growth fraction in human brain tumors defined by the monoclonal antibody Ki-67.

The monoclonal antibody Ki-67, which reacts with cells in the active part of the cell cycle, was used to evaluate immunocytochemically the growth fraction in 22 primary brain neoplasms. The percentage of labelled cells reflected the histological grade of malignancy of each neoplasms. High percentage of Ki-67-positive cells were observed in one choroid plexus carcinoma (60%), one primary melanoma of meninges (40%), three medulloblastomas (40%-50%), one anaplastic astrocytoma and six glioblastomas (10%-40%). One ependymoma had 7% positive cells. Rare positive cells (1%) were present in one pilocytic astrocytoma and one ganglioglioma. Except one negative case, the meningiomas (five cases) had values of positivity ranging from 1% to 6%. Two acoustic schwannomas were negative. These results suggest that immunocytochemical staining with the Ki-67 may be a useful method for measuring the growth fraction in brain neoplasms.

Antibodies, Monoclonal↗

Proliferative rates of non-Hodgkin's lymphomas as assessed by Ki-67 antibody.

The Ki-67 antibody, a monoclonal antibody that reacts with nuclei in actively proliferating cells, was used in an immunohistochemical study to assess the growth fractions of non-Hodgkin's lymphomas and related disorders. The lowest proliferative indices were found in small lymphocytic lymphoma/chronic lymphocytic leukemia and intermediate lymphocytic/mantle zone lymphoma. An intermediate proliferative index was seen in the follicular lymphomas and diffuse small cleaved cell and diffuse mixed cell lymphomas. A high index was seen in the diffuse large cell lymphoma and lymphoblastic lymphoma. The highest and most consistent proliferative index was seen in small noncleaved cell lymphoma. Cases of reactive follicular hyperplasia had a significantly higher proliferative index than those of follicular lymphoma. We conclude that the Ki-67 antibody has great utility in providing an estimate of the proliferative rate of non-Hodgkin's lymphomas. Prospective studies may show this information to have prognostic value independent of histologic classification.

Antibodies, Monoclonal↗

The ontogeny of the interleukin 2 receptor expression and of the interleukin 2 responsiveness in the rat thymus.

The ontogeny of the interleukin 2 receptor (IL 2 R) expression and of the IL 2 responsiveness has been investigated in the rat thymus. In tissue sections, IL 2 R-bearing cells were first detected at day 16 of gestation using the anti-IL 2 R mAb ART-18. In contrast to mice, IL 2 R-bearing cells of the rat are localized mainly in the thymic medulla from the first day of the corticomedullary compartimentalization, and not in the cortex. They are found in regions with a high expression of MHC class II antigens. The proportion of IL 2 R-bearing cells increases during gestation, reaches a peak at the first day after birth and declines to the adult level in the following weeks. The appearance of medullary localized IL 2 R-bearing cells is paralleled with the capacity of the thymocytes to proliferate in response to IL 2 without any additional stimuli.

Animals↗

Immunohistochemical determination of growth fractions in human permanent cell lines and lymphoid tumours: a critical comparison of the monoclonal antibodies OKT9 and Ki-67.

OKT9 and Ki-67 monoclonal antibodies have recently been proposed as useful tools for evaluating the growth fraction in malignant tumours, with special reference to non-Hodgkin's lymphomas. In particular, while the former is commonly thought to detect a transferrin receptor present on the cytoplasmic membrane of proliferating cells, the latter recognizes a nuclear antigen, which is expressed in G1, S, G2 and M phase of continuously cycling elements. To further verify their reliability, OKT9 and Ki-67 were applied to seven permanent cell lines (four myeloid and three B-lymphoblastoid) and 100 lymphoid tumours (70 non-Hodgkin's and 30 Hodgkin's lymphomas) phenotypically characterized on frozen sections. The results obtained showed that OKT9 and Ki-67 cannot be employed as equivalent means in assessing the growth fraction. In fact, OKT9 is directed to a transferrin receptor which is not only expressed by proliferating cells, but also by some resting elements. On the other hand, Ki-67 provides a nuclear, easily detectable positivity which is restricted to proliferating cells only. Therefore, it seems to represent the only monoclonal which can confidently be employed in the assessment of the growth fraction. Furthermore, the present study underlines that the immunocytochemical analysis of the proliferation rate in tumours gives similar information to the radionucleide uptake assay, while it represents a more sensitive method than the cytofluorimetric evaluation of the DNA content.

Antibodies, Monoclonal↗

Simultaneous staining of exponentially growing versus plateau phase cells with the proliferation-associated antibody Ki-67 and propidium iodide: analysis by flow cytometry.

The antibody Ki-67, which detects proliferating cells, was used in combination with propidium iodide, a DNA-specific dye. The double-staining method allowed discrimination of cells in the phases of the cell cycle as well as the recognition of Ki-67 staining characteristics. Suspension cultures of U937 cells were measured in exponential growth and plateau phase in nutritional deprivation. The fraction of Ki-67 positive cells was nearly 100% 2 days after dilution and 46% 7 days after dilution of the cultures. Stathmokinetic measurements with colchicine and flow cytometry measurements with the BrdU-Hoechst technique yielded close to 100% proliferation at day 2 but only 18% and 6%, respectively, at day 7. The discrepancy between Ki-67 results and the results of the two other methods is considered to be a characteristic of nutritionally deprived cells.

Antibodies, Monoclonal↗

Histiocytic necrotizing lymphadenitis without granulocytic infiltration (Kikuchi's lymphadenitis). Morphological and immunohistochemical study of eight cases.

Eight examples of histiocytic necrotizing lymphadenitis without granulocytic infiltration (Kikuchi's lymphadenitis) are described. They occurred in young or middle-aged women who usually complained of latero-cervical lymphadenopathy. Serology revealed significant titres for Epstein-Barr virus and Yersinia enterocolitica serogroup 9 in one of eight and one of six tested. All patients fully recovered within 2 months. On histological examination of the lymph nodes large foci of infiltration were observed in the cortex and/or paracortex: they consisted of variable numbers of small lymphocytes, immunoblasts, macrophages and so-called plasmacytoid T-cells; granulocytes were absent. Necrotic changes varied from single pyknotic cells to extensive areas of necrosis. Immunohistochemistry showed that within the lesion the number of macrophages was inversely proportional to the number of peripheral T-lymphocytes and 'plasmacytoid T-cells'. The latter displayed a phenotype (CD4+, CD10+, CD45+) which, in the absence of macrophage-associated antigens, seemed in keeping with their supposed lymphoid nature. In seven cases peripheral T-lymphocytes predominantly expressed the cytotoxic/suppressor phenotype, while in one remaining case a mild predominance of the helper/inducer subset was observed. In the areas with less extensive tissue necrosis, numerous T-immunoblasts expressed both markers of activation and the proliferation-associated nuclear antigen Ki-67. The results of the present study expand the spectrum of our knowledge and allow speculation as to the biology of this disease.

Adolescent↗

Novel type of proliferating lymphoplasmacytoid cell with a characteristic spotted immunofluorescence pattern.

We examined bone marrow from myeloma patients for the presence of cells with the characteristics of the clonogenic cell in the myeloma stem cell assay. We identified a novel type of cell that contained cytoplasmic immunoglobulin of the relevant idiotype located in a cytoplasmic spot. This "spotted" Ig could be located in the rough endoplasmic reticulum. Spotted cells are highly proliferative, as evidenced by the nuclear staining with the antibody Ki67, and were found in the bone marrow from most of the myeloma patients studied. This type of cell was also present in patients with immunocytomas, in some cases of benign monoclonal gammopathy, and in patients in the state of polyclonal hypergammaglobulinemia. IgG subclass distribution of so-called spotted cells and plasma cells, found in a patient with pseudo biclonal gammopathy, indicates that spotted cells are intermediate between B cells and plasma cells. Spotted cells express the B cell-associated antigens HB4 and HB6 but do not express other B cluster of differentiation antigens or plasmacytoid antigens tested.

Adult↗

Cell populations in pagetoid reticulosis: an immunological study using cell activation associated monoclonal antibodies.

The nature of the epidermal cellular infiltrate in pagetoid reticulosis is still subject to intense controversies. Using a panel of recently developed monoclonal antibodies against cell activation and proliferation associated antigens it was possible to demonstrate the activated state of numerous T cells within the lesional epidermis. Moreover approximately 10% of these T cells reacted with proliferation associated antigens. In addition macrophages and Langerhans' cells were found to represent a regular constituent of the epidermal infiltrate with a density clearly exceeding that of unaffected adjacent epidermis. The close apposition of activated T cells and monocytic cells suggests an intensive interaction of both cell types in the development of the pagetoid reticulosis lesion.

Adult↗

Value of monoclonal anti-CD22 (p135) antibodies for the detection of normal and neoplastic B lymphoid cells.

Two monoclonal antibodies (To15 and 4KB128) specific for the B cell-associated CD22 antigen (135,000 mol wt) are described. On immunoenzymatic analysis of cryostat tissue sections, these antibodies strongly label both mantle zone and germinal center B lymphoid cells in secondary lymphoid follicles (and also scattered extrafollicular lymphoid cells) but are unreactive with other cell types (with the exception of weak reactivity with some epithelioid histiocytes). These reactions differ from those of monoclonal antibodies B1 and B2 (anti-CD20 and CD21) but are similar to those of the pan-B antibody B4 (anti-CD19). One of the anti-CD22 antibodies (To15) has been tested extensively by immunoenzymatic labeling on greater than 350 neoplastic lymphoid and hematological samples. The CD22 antigen was found in tissue sections in most B cell-derived neoplasms, the major exceptions being myeloma (all cases negative) and a small proportion of high-grade lymphoma (6% of cases negative). In cell smears, the antigen could be found on neoplastic cells in most B cell lymphoproliferative disorders, including common acute lymphoblastic leukemia (ALL) (90% positive) and B cell chronic lymphocytic leukemia (CLL) (89% positive). We conclude that anti-CD22 antibodies are of value for identification of human B cell lymphoproliferative disorders (especially when used in conjunction with anti-CD19 antibodies). Previous reports that the CD22 antigen is absent from many B cell neoplasms are probably due to its being expressed within the cytoplasm of immature B cells rather than on their surface.

Antibodies, Monoclonal↗

Tumor cell growth fraction in Hodgkin's disease.

The growth fraction of tumor cells was studied in 45 cases of Hodgkin's disease by means of a recently developed double immunostaining technique using monoclonal antibody Ki-1, which reacts selectively with Hodgkin and Reed-Sternberg cells in tissues affected by Hodgkin's disease, and antibody Ki-67, which recognizes a cell proliferation-associated nuclear antigen. The medians of the growth fractions of the tumor cells in all histologic subtypes of Hodgkin's disease varied between 78% and 83%. In none of the cases investigated did we find a growth fraction below 50%. Furthermore, mononucleated Hodgkin cells as well as multi-nucleated Reed-Sternberg cells showed a similar Ki-67 labeling index, indicating that both tumor cell types belong to the proliferating pool of this malignancy.

Antibodies, Monoclonal↗