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Biomedical subjects

J Gerdes

Publications and source records attributed to J Gerdes.

At least 163 records · Page 9Linked to original sources

Growth fractions and estrogen receptors in human breast cancers as determined in situ with monoclonal antibodies.

The growth fraction (GF) and estrogen receptor (ER) status of 76 cases of breast cancer were investigated on frozen sections of the same tissue block by immunostaining with monoclonal antibodies (Ki-67 and anti ER antibody). In 55 cases of this series, the ER status was also determined by standard biochemical methods. Our study revealed an inverse correlation between GF and ER status. This negative relationship was most significant when both variables were determined immunohistologically in the same tissue block and less significant when GF was analyzed by immunohistology and ER status by biochemical methods. These data suggest that the immunohistologically assessed ER values characterize the receptor status of a given carcinoma better than the biochemical values, which leads to the conclusion that the immunohistologically determined close negative relationship between GF and ER reflects the actual in vivo situation of a given breast carcinoma case. However, the immunohistologic analysis also revealed that there is a proportion of exceptional cases, ie, those with a positive ER status and a large or moderately large GF. Because only half of the ER-positive breast carcinomas respond to endocrine therapy with objective remission., it is hypothesized that it might be preferentially these mentioned exceptional cases that fail to positively respond to endocrine treatment protocols.

Antibodies, Antinuclear↗

Description of a sequential staining procedure for double immunoenzymatic staining of pairs of antigens using monoclonal antibodies.

This paper describes a sequential staining procedure for double immunoenzymatic staining of pairs of antigens in frozen tissue sections and cell smears using monoclonal antibodies. This technique involves performance of an indirect immunoperoxidase sandwich (including development of the enzyme reaction) followed by an unlabelled immuno-alkaline phosphatase sandwich (the APAAP method). The two enzyme labels are revealed using DAB/H2O2 for peroxidase and naphthol AS-MX plus fast blue or fast red for alkaline phosphatase. When compared with a hapten-sandwich/biotin-avidin system, the sequential staining procedure proved to be simpler and more sensitive and was also more suitable for double immunoenzymatic staining when monoclonal antibodies were only available in small amounts. The sequential staining procedure is particularly useful for the identification of antigens distributed in different cell populations or in different sites (e.g., nucleus and cytoplasm or cell surface) of the same cell. In contrast, this method does not appear to be very suitable for demonstrating two antigens located in the same site (e.g., surface membrane) of the same cell for which purpose double immunofluorescence remains the first choice.

Alkaline Phosphatase↗

Determination of the growth fraction in cell suspensions by flow cytometry using the monoclonal antibody Ki-67.

A novel procedure for determining the growth fraction of cell suspensions by flow cytometry is described. This method identifies proliferating cells by binding the monoclonal antibody Ki-67 to a nuclear antigen present in all cells that are in the G1, S, G2, and M phase of the cell cycle, but not in the G0 phase. In a kinetic study of Na cell line U937 using concanavalin A for stimulation of peripheral blood mononuclear cells, a steady increase of Ki-67 positive cells evaluated by flow cytometry was observed. Simultaneously, the [3H]thymidine uptake of the ConA blasts was measured and compared to the expression of Ki-67. A linear correlation between the percentage of Ki-67 positive cells and the log transformed counts per minute was demonstrated, and staining with Ki-67 detected cell proliferation with the same sensitivity as 3H-TdR uptake. In addition, it was possible to stain Ki-67-labelled cells with a second cell marker if a second fluorescent dye coupled to an antibody was used. This provided the opportunity to define precisely the phenotype of proliferating cells. Conversely, the number of proliferating cells expressing certain preselected surface markers could be easily determined.

Antibodies, Monoclonal↗

Improved grading of bone tumors with the monoclonal antibody Ki-67.

A total of 60 bone tumors and tumor-like lesions presenting various grades of malignancy were investigated immunohistologically with the monoclonal antibody Ki-67 directed against a cell proliferation-associated nuclear antigen. The results obtained agree well with those of flow cytometric and autoradiographic studies on similar tumor entities. The monoclonal antibody Ki-67 was found to be a handy and reliable tool for improved grading of bone tumors.

Antibodies, Monoclonal↗

Staphylococcus epidermidis-associated enterocolitis.

Nineteen infants (mean +/- SD gestational age 30 +/- 2 weeks, birth weight 1.28 +/- 0.53 kg) with Staphylococcus epidermidis bacteremia were found on retrospective chart review to have had signs and symptoms of acute enterocolitis. This S. epidermidis-associated enterocolitis constituted 37% of the 51 cases of enterocolitis and 23% of the 81 cases of S. epidermidis sepsis during the study period. S. epidermidis-associated enterocolitis was relatively mild compared with other forms of enterocolitis. Although abdominal radiographs showed markedly abnormal bowel gas patterns with distended bowel loops and bowel wall edema, only one infant had pneumatosis intestinalis and none had portal venous or free intraperitoneal gas. Only three infants had neutropenia, and five had thrombocytopenia. None of these infants required surgical intervention. Although bloody stools often persisted for weeks, none of the neonates had prolonged feeding intolerance or development of a stricture. We conclude that S. epidermidis infection is commonly associated with a mild form of enterocolitis in the neonate and that this association should be considered when selecting antibiotics for therapy.

Enterocolitis↗

The value of lymph node biopsy in patients with the acquired immunodeficiency syndrome (AIDS) and the AIDS-related complex (ARC): a morphological and immunohistochemical study of 90 cases.

The morphological and immunohistochemical findings in lymph nodes of nine patients with the acquired immunodeficiency syndrome (AIDS) and 81 patients with the AIDS-related complex (ARC) are presented. Three basic histological patterns were observed: follicular hyperplasia (29 cases), mixed hyperplasia (49 cases) and lymphocyte depletion (12 cases). While the first two variants were detected in typical ARC patients, lymphocyte depletion was always associated with AIDS. Immunohistochemistry on frozen sections showed that the number of B-cells varied throughout the series, being higher in the follicular type and significantly lower in the lymphocyte depletion nodes. The content of T-lymphocytes of the helper/inducer (T4) phenotype was reduced in all instances; this reduction was more pronounced in the germinal centres in follicular hyperplasia, while it involved all compartments of the node in the mixed and lymphocyte depletion types. In contrast the cytotoxic/suppressor (T8) subset was increased in the follicular and mixed hyperplasias only. Partial disintegration of the dendritic network in at least some of the follicles could be demonstrated in all lymph nodes. In the follicular and mixed hyperplasias there was a high number of proliferating B-cells in the germinal centres. Our data indicate the usefulness of grading the changes occurring in lymph nodes of patients with ARC and AIDS, and allow speculation as to the pathophysiology of these conditions.

AIDS-Related Complex↗

New approach to assessing lung tumours in man.

One hundred and four surgically resected lung tumours were labelled in either cryostat or freeze dried sections with a monoclonal antibody (Ki67), which reacts with a nuclear antigen expressed by proliferating cells. The tumours were categorised semiquantitatively into four proliferative grades, a classification that can be performed rapidly and reproducibly by the pathologist. In keeping with previous cell kinetic studies all small cell carcinomas had high proliferation rates, whereas the carcinoid tumours were in the lowest grade. In contrast, the adenocarcinomas (27 cases) and squamous cell carcinomas (63 cases) varied widely in their proliferative state, in keeping with their heterogeneous, morphological, and clinical behaviour. Immunocytochemical labelling of lung tumour biopsy specimens with antibody Ki67 is a simple technique within the scope of routine surgical pathology laboratories, which might enable these tumours to be classified according to their proliferative status and treatment to be selected accordingly.

Adenocarcinoma↗

Growth fractions in breast cancers determined in situ with monoclonal antibody Ki-67.

The growth fractions of 160 mammary carcinomas and 30 benign mammary lesions were determined in situ by immunostaining with the monoclonal antibody Ki-67. Benign lesions had a mean value of 3% Ki-67 positive cells, whereas the mean value of mammary carcinomas was 16.6%. A comparison of the mean values of Ki-67 positive cells with the histological grade of the tumours showed a correlation between these two variables--that is, histological grade 1 showed 9%, grade 2 16%, and grade 3 26% proliferating cells. Considering the individual Ki-67 values in the different histological grades, it was evident that there was considerable scatter in the number of proliferating cells, so that the proliferation rates of grades 1, 2, and 3 overlapped each other. This indicates a dissociation between histological grade of malignancy and size of the growth fraction in most breast cancers. Follow up studies are needed to establish which of the two variables--that is, morphological degree of malignancy, or the proportion of Ki-67 positive cells--correlates better with response to treatment and survival in individual cases.

Antibodies, Monoclonal↗

High proliferative activity of Reed Sternberg associated antigen Ki-1 positive cells in normal lymphoid tissue.

An improved immunoenzymatic double labelling method was developed, which simultaneously shows the Ki-1 membrane antigen and the nuclear proliferation associated antigen, defined by monoclonal antibody Ki-67. This new approach permits in situ discrimination of cells that are proliferating or not with a particular membrane antigen. Most Ki-1 positive cells in normal lymphoid tissue also express the Ki-67 nuclear antigen and thus appear to be proliferating. As proliferating cells are more susceptible to malignant transformation than quiescent cells, it is possible that the small number of normal Ki-1 positive cells might, none the less, cause a large proportion of all lymphomas in man.

Antibodies, Monoclonal↗

An immunohistological method for estimating cell growth fractions in rapid histopathological diagnosis during surgery.

In the past, it has been impossible to carry out immunohistological staining as part of a rapid histopathological diagnosis during surgery because the available methods were too time-consuming. The present report introduces a rapid indirect immunoperoxidase method that requires only 10-12 min. Thus, the immunological characterization of tumour cells may now be applied as an additional parameter for histopathological diagnosis during surgery. In this first attempt, the monoclonal antibody Ki-67, which reacts with a human nuclear antigen present in proliferating cells and absent in quiescent cells, was applied with a new immunostaining method and the results were compared with those obtained by the more time-consuming routine immunohistological method. There was no significant difference between the percentages of Ki-67-positive cells determined with the two methods in normal or neoplastic human tissues. Since knowledge of the growth rate of a malignant tumour may be of prognostic and/or therapeutic value in individual cases, it might be useful to routinely apply this new approach for histopathological diagnosis during surgery.

Antibodies, Monoclonal↗

The expression of the Hodgkin's disease associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: evidence that Reed-Sternberg cells and histiocytic malignancies are derived from activated lymphoid cells.

Ki-1 is a monoclonal antibody (raised against a Hodgkin's disease-derived cell line) that, in biopsy tissue affected by Hodgkin's disease, reacts selectively with Reed-Sternberg cells. The expression of Ki-1 antigen has been analyzed by immunocytochemical techniques in a wide range of human tissue and cell samples, including fetal tissue, malignant lymphomas (290 cases), and mitogen- and virus-transformed peripheral blood lymphocytes. The antigen was detectable on a variable proportion of cells in all cases of lymphomatoid papulosis and angio-immunoblastic lymphadenopathy and in 28% of the cases of peripheral T cell lymphomas (including lympho-epithelioid lymphomas). It was also expressed (more strongly) on tumor cells in 45 cases of diffuse large-cell lymphoma, most of which had originally been diagnosed as malignant histiocytosis or anaplastic carcinoma, because of their bizarre morphology. However, all of these cases lacked macrophage and epithelial antigens. Thirty-five cases expressed T cell-related antigens (associated in nine cases with the coexpression of B cell-related antigens), seven bore B cell-related antigens alone, and three were devoid of T and B cell markers. DNA hybridization with a JH specific probe showed a germline configuration in 11 cases of T cell phenotype, in two cases lacking T and B cell antigens, and in one case of mixed T/B phenotype, while rearrangement was found in two cases of clear B cell type and in one mixed T/B case. Expression of the Ki-1 antigen could be induced, together with interleukin 2 (IL 2) receptor, on normal lymphoid cells of both T and B cell type by exposure to phytohemagglutinin, human T leukemia viruses, Epstein-Barr virus, or Staphylococcus aureus. The results obtained indicate that Ki-1 antigen is an inducible lymphoid-associated molecule that identifies a group of hitherto poorly characterized normal and neoplastic large lymphoid cells. Tumors comprised solely of these cells show both morphological and immunological similarities to the neoplastic cells in Hodgkin's disease. This suggests that both disorders represent the neoplastic proliferation of activated lymphoid cells of either T cell or, less commonly, B cell origin. Disorders in which only a minority of cells express Ki-1 antigen (lymphomatoid papulosis, angio-immunoblastic lymphadenopathy, and certain T cell lymphomas) probably represent lesions in which only some of the abnormal cells have transformed into an "activation state." In direct support of this view is the finding that the Ki-1 expression in these lesions is accompanied by the expression of HLA-DR and IL 2 receptors.

Adolescent↗