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F Momburg

Publications and source records attributed to F Momburg.

At least 91 records · Page 5Linked to original sources
PubMed1988

Non-co-ordinate expression of HLA-DR antigens and invariant chain.

The expression of HLA-DR and MHC class II antigen-associated invariant chain (Ii) was studied in normal colorectal mucosa, adenomas and carcinomas using monoclonal antibodies and a sensitive immunoperoxidase technique on frozen sections. In six of 15 specimens of normal mucosa, epithelial cells expressed Ii, but were unreactive for HLA-DR antigens. In 15/20 adenomas and 51/70 carcinomas, Ii-positive tumour cells clearly outnumbered HLA-DR-positive tumour cells. Expression of Ii in non-neoplastic epithelium adjacent to carcinoma was much stronger than expression of HLA-DR. The results indicate that in certain tissues expression of these two antigens is not closely associated.

Adenoma↗
PubMed1987

The influence of major histocompatibility complex class I antigens on tumor growth and metastasis.

The work described here demonstrates the importance of major histocompatibility complex class I antigens for the control of tumor growth and metastasis by the host's immune system. In certain murine tumor cells which have lost expression of H-2 class I antigens, a de novo expression of H-2 can be achieved by transfection with syngeneic class I genes. In contrast to the parental cells the transfected tumors do not grow any more in syngeneic mice, or in other cases they do not form metastases. The studies suggest that the de novo expression of the H-2 antigens renders the tumors highly immunogenic and leads to effective recognition of a tumor-associated antigen in conjunction with the transfected H-2 antigen. These conclusions were confirmed in other tumor systems. For example, separation of a heterogeneous tumor into clones expressing high or low amounts of H-2 showed that only the tumor cell with low H-2 grew well in syngeneic mice, whereas the H-2 high tumor clones were rejected. In other studies in vitro induction by IFN-gamma of H-2 antigen on H-2 negative tumors led to reduced tumor growth in vivo which was due to the increased immunogenicity. About 10% of human tumors are also low or defective for HLA class I expression and often these tumors appear to be more malignant. The class I negative tumors could either have arisen from class I low or negative tissues or are HLA loss variants which escaped the attack of the immune system. Altogether, our studies and the data of other laboratories demonstrate the important role of class I antigens for anti-tumor immunity and they suggest that modulation of class I expression by gene transfection or by induction with soluble mediators could be a useful tool for the manipulation of tumor immunity.

Animals↗
PubMed1987

B-cell lymphomas of high-grade malignancy frequently lack HLA-DR, -DP and -DQ antigens and associated invariant chain.

The expression of HLA-DR, HLA-DP and HLA-DQ antigens was studied in an unselected series of 66 B-cell lymphomas by means of immunohistology using monoclonal antibodies against non-polymorphic determinants in a sensitive immunoperoxidase technique. In addition, the expression of the MHC class-II antigen-associated invariant chain (li) was examined. The tumors were classified according to the Kiel classification, 30 being of high-grade and 36 being of low-grade malignancy. Only 6 lymphomas of high-grade and 16 lymphomas of low-grade malignancy showed coordinate strong expression of all HLA class-II antigens and invariant chain as observed in the normal peripheral B cell. Six further tumors of high-grade and 8 tumors of low-grade malignancy contained tumor-cell subsets with reduced expression of one or several of the antigens. Eighteen lymphomas of high-grade and 12 lymphomas of low-grade malignancy contained varying tumor-cell subsets that were negative for HLA-DR, -DP, -DQ and li in a selective or combined manner. Three highly malignant tumors were devoid of all class-II antigens and li; 2 highly malignant tumors expressed invariant chain only. The presence of high-grade malignancy was significantly correlated with the occurrence of tumor cells lacking HLA-DR (p = 0.004), HLA-DP (p = 0.013), HLA-DQ (p = 0.007) or li (p = 0.024).

B-Lymphocytes↗
PubMed1987

Defective expression of MHC class I antigens is frequent in B-cell lymphomas of high-grade malignancy.

An unselected series of 66 immunohistologically proven B-cell lymphomas was examined for the expression of MHC class I antigens with monoclonal antibodies directed against non-polymorphic determinants of HLA-A,B,C heavy chain and beta 2-microglobulin. The tumors were classified according to the Kiel classification. No significant differences were observed in the reaction for HLA-A,B,C and beta 2m which may be indicative of a coordinate expression in our lymphoma series. In 37 cases (56%), all tumor cells exhibited strong staining for class I antigens as observed in normal B cells. The remaining 29 cases (44%) showed abnormally low or undetectable class I expression in varying tumor cell subsets; 13 cases were completely devoid of HLA-A,B,C. Twenty-two out of 30 lymphomas of high-grade malignancy but only 7/36 lymphomas of low-grade malignancy presented defective class I expression. This difference in proportion is highly significant (p less than 0.00002). Eleven of the 13 class I-negative lymphomas belonged to the group of high-grade malignancy. Centrocytic lymphoma, which has the poorest prognosis among the B-cell lymphomas of low-grade malignancy, was defective in 40% of the cases examined. The lymphoblastic type represented an exception within the lymphomas of high-grade malignancy as no defective expression was observed. In addition to the correlation between the high-grade malignancy and defective class I expression, defects occurred more frequently in lymphomas with an extra-nodal primary manifestation (p less than 0.05). The grade of malignancy, however, was not correlated with the primary site of the lymphoma.

Antibodies, Monoclonal↗
PubMed1987

Immunohistochemical study of the expression of a Mr 34,000 human epithelium-specific surface glycoprotein in normal and malignant tissues.

Monoclonal antibody HEA125 was used to study the tissue distribution of an epithelial cell surface glycoprotein of Mr 34,000 (Egp34). A large panel of normal and neoplastic tissues was examined for immunoreactivity with HEA125 by means of a sensitive immunoperoxidase technique. HEA125 labeled most epithelial cell types throughout the body but did not label any nonepithelial tissue. Major exceptions were epidermal keratinocytes, gastric parietal cells, hepatocytes, thymic cortical epithelial, and myoepithelial cells. Normal mesothelial cells were unreactive. In normal glandular epithelia and tubular adenocarcinomas exclusively the basolateral cell membranes were stained. HEA125 intensely reacted with all tested carcinoma specimens derived from colorectum, stomach, pancreas, liver, lung, mammary gland, ovary, thyroid, kidney, urinary bladder, and prostate including a number of anaplastic, diffusely infiltrating carcinomas. Metastatic lesions of these tumors were consistently positive. Generally, the staining of tumor cells was very homogeneous. The majority of squamous cell carcinomas were less strongly labeled than adenocarcinomas; keratinizing areas of the tumor masses were negative. Germ cell tumors and mesotheliomas of epithelioid type focally expressed the antigen. Egp34 was found to be absent from sarcomas, lymphomas, melanomas, and neurogenic tumors. Hence, HEA125 is a useful reagent for the distinction of carcinomas from nonepithelial neoplasms, even at very low degrees of histological differentiation. Furthermore, HEA125 allows the immunohistochemical detection of micrometastases originating from carcinomas. The antigen is detectable in formalin-fixed paraffin sections.

Antibodies, Monoclonal↗
PubMed1987

Phenotype of stromal cell-associated thymocytes in situ is compatible with selection of the T cell repertoire at an "immature" stage of thymic T cell differentiation.

Murine thymocytes interacting with cortical macrophages, cortical epithelial cells and medullary dendritic cells in situ express T cell receptors at low to intermediate density. They co-express the lineage markers Lyt-2 and L3T4 and are not enriched for cells expressing high-density interleukin 2 and lymph node homing receptors. Thus, recognition of stromal cells in situ in distinct thymic microenvironments occurs at a common stage of T cell maturation which is phenotypically intermediate between intrathymic precursor cells and mature medullary-type thymocytes. The surface phenotype of dendritic cell-associated thymocytes indicates the presence of thymocytes with a "cortical" phenotype within the antigen-exposed ("nonsterile") phase of T cell maturation in the medulla.

Animals↗
PubMed1987

Epithelium-specific surface glycoprotein of Mr 34,000 is a widely distributed human carcinoma marker.

An epithelial cell surface antigen is described which is defined by monoclonal antibody HEA125 (IgG1). The antibody was raised against the colon carcinoma cell line HT-29. Under reducing conditions HEA125 immunoprecipitates a surface glycoprotein of Mr 34,000 which was designated Egp34. The antigen does not contain disulfide-linked subunits. A slightly different migration behavior under non-reducing conditions (Mr 39,000) may be due to intrachain disulfide bonds. After enzymatic cleavage of N-linked carbohydrate residues the apparent molecular weight of the antigen was 29,000. Egp34 is a major cell surface component of HT-29 cells (10(6) molecules per cell). No antigen could be detected in the sera of colorectal cancer patients. A panel of malignant cell lines and normal cells was studied for surface expression of the antigen. 17/17 carcinoma lines of 6 different origins expressed the antigen, whereas 16/16 melanoma, neuroblastoma, sarcoma and lymphoma/leukaemia were unreactive as it was the case for normal fibroblasts and blood cells. Immunoperoxidase staining of frozen tissue sections with HEA125 demonstrated the presence of Egp34 in almost all normal epithelia and tumours derived therefrom. No reactivity with non-epithelial tissues was observed. Undifferentiated carcinomas of various origins homogeneously expressed Egp34. Therefore, HEA125 may become a valuable tool for the immunohistochemical diagnosis of carcinoma.

Animals↗
PubMed1987

Mediastinal lymphoma of clear cell type is a tumor corresponding to terminal steps of B cell differentiation.

This article reports eight primary mediastinal tumors occurring in young adults (19 to 43 years, mean 29.4 years), predominantly female (six of eight) adults. Most patients responded badly to aggressive therapy. Progression is presently noted in one patient; five patients died 10, 11, 13, 18, and 22 months after diagnosis. No patient developed leukemia. The tumors were highly proliferative, had a diffuse growth pattern, and comprised clear cells of variable size. They could not be classified histologically, but could, however, be immunohistologically characterized as B cell lymphomas. In all cases, the immunophenotype was LC+, cALLa-, CD19+, CD20+, CD21-, Ig (surface/cytoplasm)-, and PC-1+. In addition, the neoplastic cells exhibited variable defects in the expression of HLA-A,B,C and HLA-DR and inconstant expression of other B cell-restricted/associated antigens. This combination of immunophenotypical and clinical features suggests that the mediastinal clear cell lymphoma (MCCL) is a previously undescribed type of B cell lymphoma corresponding to the terminal steps of B cell differentiation.

Adult↗
PubMed1987

Sequential induction of MHC antigens on autochthonous cells of ileum affected by Crohn's disease.

Changes were examined in the expression of Class I and II major histocompatibility complex (MHC) antigens by autochthonous cells of the terminal ileum affected by Crohn's disease. The study was based on the analysis of transmural specimens from terminal ileum segments obtained in the course of ileocolectomy for colon cancer and Crohn's disease. Serial sections were immunostained using monoclonal antibodies directed against monomorphic determinants of HLA-A,B,C, DR, DP, DQ, and the invariant chain (Ii) associated with Class II molecules. Compared with the normal state, the only change in Class I antigen expression occurring in Crohn's disease was the induction of HLA-A,B,C antigens in lymphatic endothelium. Changes in Class II antigen expression were more substantial. Enhancement of HLA-DR expression was found in enterocytes; DR induction was observed in glial cells of the visceral nervous plexus and in venular and venous endothelium. HLA-DP and DQ antigens were induced in enterocytes, glial cells, and capillary and venular endothelium, although this induction was restricted to areas of moderate or high inflammatory activity. The tissue distribution of Ii closely resembled that of HLA-DR, although this association was not strict: on the one hand, arterial endothelium contained low amounts of Ii in the absence of DR antigens; on the other hand, glial cells expressed Class II molecules in the absence of Ii. The extent of local enhancement/induction of MHC antigens was positively correlated with the local density of the cellular infiltrate. These data suggest that altered MHC antigen expression by autochthonous structures might be mediated by factors released from the lymphohistiocytic infiltrate, which is itself attracted by an unknown signal. In conjunction with an unknown antigen, the enhanced expression of Class II antigens might trigger an autoaggressive immune response.

Adolescent↗
PubMed1986

Loss of HLA-A,B,C and de novo expression of HLA-D in colorectal cancer.

One hundred primary colorectal carcinomas and 19 metastases were studied for the expression of HLA-A,B,C and HLA-D antigens using monoclonal antibodies (MAbs) against framework determinants and a sensitive immunoperoxidase technique on frozen sections. With MAb W6/32, 65 tumors were intensely stained for HLA-A,B,C; 22 showed a reduced staining intensity, in 5 carcinomas a minor or major subset of the tumor cells lacked HLA-A,B,C, and in 8 cases all tumor cells were unreactive. The loss of HLA-A,B,C was inversely correlated with the degree of differentiation. No relation was found to type, stage and site of the tumor, or to age and sex of the patients. With MAb 2.06, 58 tumors were HLA-D negative, 20 exhibited small positive foci, 19 showed a patchy staining pattern, and 3 were homogeneously HLA-D positive. There was no apparent correlation between HLA-D expression and any of the clinico-pathological features mentioned, nor was it related to the loss of HLA-A,B,C. About half of the metastases displayed the same staining pattern for HLA-A,B,C and -D as the respective primary tumors. The remainder differed from the primary carcinoma by gain or loss of HLA antigens.

Adult↗
PubMed1986

Differential expression of Ia and Ia-associated invariant chain in mouse tissues after in vivo treatment with IFN-gamma.

B10.BR mice were injected i.v. with varying doses of recombinant IFN-gamma on three consecutive days. In tissue sections of 13 organs, the distribution of Ia antigens and Ia-associated invariant chain (Ii) was studied by using an immunoperoxidase technique. In the control animal, Ia and Ii were shown to be co-expressed in most tissues. However, on Kupffer cells, a small number of hepatocytes, and a subset of lymphocytes in lymph nodes and in the splenic red pulp only Ii, and no Ia, was detectable. In contrast, strongly Ia+ interdigitating reticulum cells of T-dependent areas of lymph nodes and spleen were only weakly stained for Ii. IFN-gamma treatment resulted in a dramatic increase of MHC antigen expression throughout the body, with striking differences in the inducibility of certain tissues for Ia and Ii: Bronchial epithelium was clearly induced to express the invariant chain, whereas Ia antigens remained entirely absent. Moreover, in kidney tubules and colon epithelium, Ii was induced more broadly than Ia. In contrast to the induction of Ii on endothelial cells of larger vessels in kidney, heart, and lungs, no de novo expression of Ia or Ii in capillary endothelial cells was observed. The number of detectable Ia+/Ii+ interstitial dendritic cells considerably increased upon exposure to IFN-gamma. Neither neurons nor glial cells were induced to MHC antigen expression. Our data demonstrate that IFN-gamma applied i.v. is a potent inducer or enhancer of Ia antigens and invariant chain in a variety of cell types.

Animals↗
PubMed1986

In vivo induction of H-2K/D antigens by recombinant interferon-gamma.

B10.BR mice received i.v. increasing doses of recombinant interferon-gamma (rIFN-gamma) on three consecutive days. Using an immunoperoxidase technique the distribution of H-2K/D antigens was studied in frozen tissue sections of thirteen organs (kidney, liver, pancreas, esophagus, stomach, small intestine, colon, lungs, heart, brain, thymus, lymph node and spleen). Class I antigens were shown to be induced or enhanced in almost every organ after exposure to IFN-gamma. This effect was particularly conspicuous for renal tubular cells, hepatocytes, bronchiolar epithelial cells, gastric mucous cells, thymic cortical lymphocytes and capillary endothelial cells in heart and kidney. Neurons, glial cells, gastric chief and parietal cells, and pancreas cells were not inducible. The findings show that i.v. application of IFN-gamma leads to strong induction or enhancement of major histocompatibility complex class I antigens in a wide variety of tissues.

Antibodies, Monoclonal↗
PubMed1986

Simultaneous demonstration of lectin-binding sites and antigens detected by monoclonal antibodies in a parallelized double-staining technique: a highly discriminative and quickly developing technique for frozen sections.

A sensitive immunoenzymatic double-staining technique is presented for the simultaneous visualization of lectin-binding sites and antigenic structures detected by monoclonal antibodies. The lectin is demonstrated by an extended unlabeled peroxidase-antiperoxidase (PAP) technique and the monoclonal antibody by an alkaline phosphatase-antialkaline phosphatase (APAAP) method, which corresponds to the standard PAP technique. 3-amino-9-ethylcarbazole (AEC) and fast blue BB salt serve as substrates for the peroxidase and the alkaline phosphatase, respectively. The antisera and the enzyme complexes raised in different animals enable the performance of three parallel incubation steps. The staining procedure requires three and a half hours altogether. This method proved to be highly discriminative and rather insensitive to interference by various artifacts.

Antibodies, Monoclonal↗
PubMed1986

The primary mediastinal clear cell lymphoma of B-cell type has variable defects in MHC antigen expression.

Eight cases of the recently reported 'primary mediastinal clear cell lymphoma of B-cell type' (Möller et al., 1986) were examined immunohistologically for the expression of cytoplasmic and/or surface antigens of MHC class I and II with mAbs directed against framework determinants of HLA-A,B,C (W6/32; B9.12.1), HLA-DP,DR,DQ (2.06), -DQ (Leu 10; Tü22), -DR (Tü34) gene products, and with mAbs specific for beta 2-microglobulin (BBM-1) and the HLA-D associated invariant chain (Vic-Y1). Besides the reported Ig-deficiency, the neoplastic B-cells of 7/8 tumours have variable defects in MHC antigen expression. Three lack both class I and class II antigens, one tumour lacks class I antigens but expresses HLA-DQ and -DR on the majority of neoplastic cells, three others contain varying proportions of MHC-antigen deficient tumour cells. The expression of Ii is closely correlated with HLA-D(R) expression and its antigenic sites are strictly located in the cytoplasm. Against the background of current knowledge, the variable and occasionally severe defects in MHC antigen expression within the herein presented series of B-cell lymphomas suggest that this unusual feature might be another characteristic of a novel lymphoma type.

Adult↗
PubMed1986

[Immunohistologic analysis of chronic obstructive sialadenitis. I. Changes in the expression of antigens of the major histocompatibility complex].

In the course of electrolyte sialadenitis progressing towards obstructive sialadenitis, changes in the epithelial expression of antigens of the major histocompatibility complex (MHC) occur even before morphological alterations and inflammatory cells can be detected. Class I antigens are enhanced and induced, and Class II antigens are induced. These changes begin focally. Only the expression of HLA-A,B,C and -DR in acinar epithelium is linked to the close vicinity of lymphohistiocytic infiltrates. In later stages of the disease the foci tend to fuse and antigenic changes are pronounced in areas of fibrosclerosis and parenchymal atrophy. The altered MHC antigen expression induced by chronical saliva congestion probably represents an important part of the postulated "immunoreaction in the duct epithelium" supposedly giving rise to this type of immunosialadenitis.

Adult↗