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1.
Clin Genet ; 86(4): 361-6, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24116836

ABSTRACT

Epilepsy is a common finding in patients with chromosomal macro- and micro-rearrangements but only few aberrations show a constant pattern of seizures. DNA array-based studies have reported causative copy number variations (CNVs) in 5-30% of patients with epilepsy with or without co-morbidities. The interpretation of many of the detected CNVs remains challenging. In order to identify CNVs carrying epilepsy-related genes we investigated 43 children with various patterns of epileptic seizures, intellectual disability (ID), and minor dysmorphism, using the Illumina® Infinium Human1M-DuoV1 array. In three patients we found likely causative de novo CNVs, i.e. deletions in 1q41q42.12 (3.4 Mb) and 19p13.2 (834 kb), and a mosaic two-segment duplication in 17p13.2 (218 kb) and 17p13.1 (422 kb). In six additional patients there were aberrations (a deletion in one and duplications in five patients) with uncertain clinical consequences. In total, the finding of causative chromosomal micro-rearrangements in 3 out of 43 patients (7%) and potentially causative CNVs in 6 additional patients (14%) with epilepsy and ID but without major malformations confirms the power of DNA arrays for the detection of new disease-related genetic regions.


Subject(s)
Chromosome Aberrations , Congenital Abnormalities/genetics , DNA Copy Number Variations/genetics , Epilepsy/genetics , Intellectual Disability/genetics , Child , Child, Preschool , Female , Humans , Infant , Karyotype , Male , Oligonucleotide Array Sequence Analysis/methods , Phenotype , Polymorphism, Single Nucleotide/genetics
2.
Neuropediatrics ; 43(5): 240-8, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22936351

ABSTRACT

BACKGROUND: Acute cerebellitis (AC) is characterized by cerebellar symptoms and magnetic resonance imaging (MRI) changes primarily confined to the cerebellum. OBJECTIVE: To analyze the neurological and cognitive long-term outcome of children with AC. METHODS: Children with AC diagnosed by typical clinical features and MRI findings were included in this retrospective study. Medical charts were reviewed and neurological deficits were assessed by neurological examination or by the expanded disability status scale telephone interview. Cognitive outcome was evaluated with a parental questionnaire (Kognitive Probleme bei Kindern und Jugendlichen). RESULTS: A total of 11 children (6 boys, 5 girls; age range: 3 years to 14 years and 10 months) were included. Of them, six children had a severe disease manifestation including mental status changes and neurological symptoms. Of the rest, two children had a moderate and three children had a mild form of AC. MRI of the cerebellum was obtained in the acute phase revealing signal alterations with different patterns. The average follow-up period was 4 years and 4 months. A complete recovery was observed in five children. Neurological sequelae were reported in five children ranging from ataxia to mild tremor. Cognitive deficits were found in six patients. The affected areas of cognition did include spatial visualization ability, language skills, and concentration. CONCLUSION: Neurological and cognitive sequelae are common in children with AC and underline the role of the cerebellum in cognition.


Subject(s)
Cerebellum/pathology , Encephalitis/pathology , Adolescent , Anti-Bacterial Agents/therapeutic use , Child , Child, Preschool , Cognition Disorders/etiology , Encephalitis/complications , Encephalitis/drug therapy , Female , Humans , Longitudinal Studies , Magnetic Resonance Imaging , Male , Neurologic Examination , Neuropsychological Tests , Predictive Value of Tests , Statistics as Topic , Treatment Outcome
3.
Neuropediatrics ; 40(5): 211-7, 2009 Oct.
Article in English | MEDLINE | ID: mdl-20221956

ABSTRACT

BACKGROUND: Acute disseminated encephalomyelitis (ADEM) is an acute, inflammatory-demyelinating disorder of the CNS with a favourable outcome in the majority of cases. OBJECTIVE: The aim of this study was to examine the long-term outcome of children with an initially severe form of ADEM. METHODS: Children with ADEM according to the criteria of the International Pediatric MS Study Group (IPMSSG) referred to the rehabilitation centre Vogtareuth were included. Neurological impairment was evaluated with a standardized telephone-based interview assessing the EDSS score. Neuropsychological outcome was assessed with review of the medical records and a standardized parental questionnaire (KOPKIJ). RESULTS: Twelve children (1 year 9 months to 13 years of age) were included. All children had focal-neurological signs and changes in mental status at presentation and an MRI of the brain showing a range of white and gray matter lesions. 11/12 patients with a mean follow-up of 6.2 years (2-13.6 years) had a monophasic course of the disease. One child had a multiphasic ADEM. Two children had an EDSS score of 0, three an EDSS of 2, five an EDSS between 3 and 5 and two children had an EDSS score of 6 and 9. Results of a standardized parental questionnaire (KOPKIJ) revealed that 7 children had deficits in the categories alertness, memory, school performance, visual-spatial skills and/or impulse control. CONCLUSION: The results of our study indicate that children with an initially severe manifestation of ADEM continue to have in the majority of cases neurological and neuropsychological handicaps.


Subject(s)
Cognition Disorders/etiology , Encephalomyelitis, Acute Disseminated/complications , Encephalomyelitis, Acute Disseminated/diagnosis , Adolescent , Brain/pathology , Child , Child, Preschool , Cognition Disorders/diagnosis , Cohort Studies , Female , Humans , Infant , Magnetic Resonance Imaging/methods , Male , Neurologic Examination/methods , Neuropsychological Tests , Spinal Cord/pathology
4.
Biomed Biochim Acta ; 50(12): 1261-7, 1991.
Article in English | MEDLINE | ID: mdl-1824544

ABSTRACT

In the experiments presented here 22 monoclonal antibodies (MoAbs) were produced which reacted with the tumor marker carcinoembryonic antigen (CEA). Eleven of the MoAbs reacted neither with peripheral blood granulocytes nor with purified spleen NCA-60 kDa and were therefore regarded as "CEA-specific". Only three antibodies of this group reacted exclusively with CEA-180 kDa. Eight MoAbs reacted with CEA-180 kDa and with CEA-like substances of lower molecular mass (of 160 kDa and/or 120 kDa) present in colon carcinoma cells as determined by immunoblotting. These molecules seem to be different from the classical non-specific cross-reacting antigens (NCAs) present in peripheral blood granulocytes. In contrast to that, the other 11 anti-CEA MoAbs recognized in addition to CEA-180 kDa also NCAs on granulocytes. Six of them were reactive with a purified spleen NCA-60 kDa preparation. These MoAbs bound also to reduced and alkylated CEA-180 kDa (CEA r/a), i.e. they recognize sequential epitopes. All 22 MoAbs reacted with CEA expressed in different human tumor cell lines as determined by immunocytological analysis. But six of them did not bind to the surface of these cells when tested in a radioimmuno-binding assay. It was concluded that the epitope(s) recognized by these antibodies are involved in cell membrane anchoring of the CEA-molecules.


Subject(s)
Antibodies, Monoclonal , Carcinoembryonic Antigen/analysis , Carcinoembryonic Antigen/immunology , Carcinoembryonic Antigen/isolation & purification , Cell Line , Colonic Neoplasms/chemistry , Cross Reactions , Female , Granulocytes/immunology , Humans , Immunoblotting/methods , Immunoglobulin G/classification , Immunohistochemistry , Liver Neoplasms/chemistry , Liver Neoplasms/secondary , Molecular Weight , Neoplasms , Radioimmunoassay/methods
5.
Zentralbl Allg Pathol ; 135(3): 281-5, 1989.
Article in German | MEDLINE | ID: mdl-2672678

ABSTRACT

An antiserum against human thyroglobulin isolated by gelfiltration from the human thyroid gland was raised in rabbits. The specificity of the antiserum to detect human thyroglobulin was determined by an immunoperoxidase technique on formalin-fixed and paraffin-embedded tissue sections of 17 primary thyroid carcinomas and 80 carcinomas of other origins, such as pancreas, colon, breast, bladder, ovary, testis, and larynx. Positive reactions to immunological staining were recorded only from differentiated thyroid carcinomas, while no reactions were exhibited by the other malignant tumours tested in this study.


Subject(s)
Adenocarcinoma/analysis , Carcinoma, Papillary/analysis , Thyroglobulin/analysis , Thyroid Neoplasms/analysis , Animals , Humans , Immune Sera/immunology , Immunoenzyme Techniques , Immunohistochemistry , Male , Rabbits
6.
Zentralbl Allg Pathol ; 134(6): 539-45, 1988.
Article in German | MEDLINE | ID: mdl-3213287

ABSTRACT

Monoclonal antibodies were used in an indirect immunoperoxidase assay to investigate 83 smears of pleural or peritoneal effusions for expression of the epithelial markers MAM-6, MAM-3, and carcinoembryonic antigen (CEA). All but one smears containing tumor cells according to the evaluation of H&E preparations were positive for one, two or all three markers, the exception being a malignant melanoma. Three of 5 cases, suspicious by routine cytology, exhibited marker expression in a different number of cells and thus confirmed the cytological diagnosis. Five of 63 cytologically negative smears exhibited single cells or small cell clusters positive for up to three markers. Four of these patients were found to suffer from metastatic cancer, as established by clinical follow-up and subsequent biopsy or autopsy, respectively. Felty's syndrome and concomitant serositis were diagnosed and confirmed by autopsy in one of the MAM-6 positive cases with negative cytology. The comparatively strong MAM-6 expression in some mesothelial cells of this patient might have been induced by abnormal stimulation due to the rheumatic disease. The results of this study encourage wider use of immunocytochemistry as an adjunct to cytological diagnosis in effusions.


Subject(s)
Ascitic Fluid/metabolism , Carcinoembryonic Antigen/metabolism , Membrane Glycoproteins/metabolism , Pleural Effusion/metabolism , Ascitic Fluid/analysis , Biomarkers/analysis , Humans , Immunohistochemistry/methods , Mucin-1 , Neoplasms/diagnosis
7.
Int J Cancer Suppl ; 3: 38-44, 1988.
Article in English | MEDLINE | ID: mdl-2463227

ABSTRACT

Fourteen monoclonal antibodies (MAbs) to epithelial sialomucins were studied for their immunohistochemical reactivity on serial sections of 14 formalin-fixed and paraffin-embedded adenolymphomas of the parotid gland. Two types of reactivity were observed, suggesting different cellular distribution of the corresponding epitopes. Most antibodies reacted with the luminal membrane of the columnar tumor cells (type-A reaction). The other reaction (type B) was observed with the membrane of basal epithelial cells. The antibodies could be ranked according to their tendency to show type-A and/or type-B reactions. MAb Cal was the only one with a pure type-A reaction. A strong tendency to type-A reactivity (with traces of type-B reactions) was observed for the antibodies HMFG-2, M8, E29 and NCRC-II. Several antibodies gave good type-B reactions in addition to strong type-A reactivity (MAbs 126E7, 115G2, 115D8, 140C1, F36/22, 139H2). MAb DF3 showed equally strong reactions with both cell types. A clear-cut preference of the reactions with basal cells was seen with the antibodies HMFG-1 and 115F5. This subclassification of the antibodies is in accordance with epitope mapping data, obtained by conventional blocking studies reported in the literature.


Subject(s)
Adenolymphoma/immunology , Antibodies, Monoclonal , Epitopes/analysis , Mucins/immunology , Parotid Neoplasms/immunology , Epithelium/analysis , Humans , Sialomucins
8.
Lab Invest ; 57(2): 193-9, 1987 Aug.
Article in English | MEDLINE | ID: mdl-3613527

ABSTRACT

MAM-6 antigen is detectable in a large variety of formalin fixed and paraffin embedded normal and neoplastic tissues throughout the body with some exceptions. One such exception is the large intestine in which normal mucosa has been found negative for MAM-6, while colorectal carcinomas express the antigen in almost all cases. We examined the expression of MAM-6 in 147 benign epithelial tumors (adenomas) of the colorectum and compared this with the detectability of the antigen in 123 colorectal cancers and in 108 non-neoplastic mucosa specimens. The tissue samples were subjected to an indirect immunoperoxidase assay applying the MoAb 115D8 which recognizes the epitope "a" of MAM-6. A majority of the carcinomas (99.2%) and of the adenomas (61.4%) exhibited reactivity for MAM-6 "a", whereas only 8 of the 108 non-neoplastic biopsy specimens (= 7.4%) exhibited faint focal staining. In adenomas, positive reactions were only seen in highly dysplastic tissue areas, in part reflecting carcinomata in situ. The reactivity in four non-neoplastic tissue samples could be explained by shedding of the antigen from carcinomas into glandular structures of the mucosa. Two out of 32 cases exhibiting severe colitis were also focally positive. The detectability of MAM-6 "a" in routinely processed specimens from the large intestine is therefore considered as being closely associated with malignant and premalignant processes. According to a limited study with the antibodies 139H2 and 140C1, this holds true for two additional MAM-6 epitopes. MAM-6 might be considered as a marker of severe (premalignant) dysplasia in adenomas of the large intestine. Further studies are needed to clarify if there is a biological (possibly prognostic) difference between MAM-6 positive and negative high epithelial atypia in these adenomas.


Subject(s)
Adenocarcinoma/immunology , Adenoma/immunology , Antigens, Neoplasm/analysis , Colon/immunology , Colonic Neoplasms/immunology , Membrane Proteins/analysis , Rectal Neoplasms/immunology , Antibodies, Monoclonal/immunology , Antibodies, Neoplasm/immunology , Antigens, Neoplasm/immunology , Colitis/immunology , Humans , Intestinal Mucosa/immunology , Membrane Proteins/immunology , Mucin-1 , Neoplasm Proteins/analysis , Neoplasm Proteins/immunology
9.
Microbiol Immunol ; 31(7): 665-74, 1987.
Article in English | MEDLINE | ID: mdl-2830473

ABSTRACT

Peroxidase-labeled Fab' fragments of rabbit antisera against gp52 (major envelope protein) and A-particles of mammary tumor virus (MTV) were prepared and used for investigation by immunoelectron microscopy of the replication cycle of MTV-specific envelope and core antigens in normal and malignant mammary gland cells of female mice. The specificity of the antisera was proven by absorption tests and lack of reactivity to MTV-free mammary tissues. Periodate-lysine-paraformaldehyde (PLP) fixation sufficiently preserved the antigenicity of gp52, while Zamboni's fixative was useful to preserve the core antigen. Saponin pretreatment was necessary to reveal the intracellular antigen of A particles but had no influence on gp52. In addition to its presence at the envelope of D particles, gp52 was clearly associated with the biomembrane system, including the nuclear membrane, endoplasmic reticulum, Golgi apparatus and plasma membrane independent of the presence of virus particles. In mammary tumors, a significant level of gp52 antigen was often expressed on the entire cell surface membrane. In contrast, it was localized only to the apical plasma membrane in normal mammary gland cells. A particle antigens were confined to the intracytoplasmic A particles, usually visible as clusters, and to the inner part of B particles. These ultrastructural findings support the available biochemical data on the morphogenesis of MTV particles.


Subject(s)
Antigens, Neoplasm/immunology , Antigens, Viral, Tumor/analysis , Mammary Glands, Animal/microbiology , Mammary Neoplasms, Experimental/microbiology , Mammary Tumor Virus, Mouse/immunology , Animals , Antigens, Neoplasm/analysis , Female , Mammary Glands, Animal/immunology , Mammary Neoplasms, Experimental/immunology , Mammary Tumor Virus, Mouse/ultrastructure , Mice , Mice, Inbred Strains , Virus Replication
10.
Biomed Biochim Acta ; 46(1): 143-9, 1987.
Article in English | MEDLINE | ID: mdl-2437901

ABSTRACT

Two out of five determinants recognized by monoclonal antibodies (MoAbs) on carcinoembryonic antigen (CEA) were analyzed by blocking the CEA-MoAb interaction with 9 different lectins in a solid phase radioimmunoassay. Two batches of CEA were first studied for their binding to lectins at the solid phase. Lotus, soybean and wheat germ lectins were most active, but the reaction pattern was different with the two CEA batches. The corresponding sugars were capable of inhibiting the lectin-CEA binding. MoAbs were fixed to the solid phase, and their reaction with CEA was tried to be blocked by preincubating the antigen with lectins. Lotus lectin and wheat germ agglutinin were clearly blocking the MoAb-CEA interaction, but this was strikingly dependent on the CEA batch used and the particular CEA determinant investigated. These reactions could not be blocked by sugars. The data provide evidence for a role of sugars in the sterical configuration of CEA determinants. In view of the heterogeneity of the findings, however, the conclusion is drawn that the protein moiety plays the more important role in the configuration of the CEA determinants studied.


Subject(s)
Carbohydrates/analysis , Carcinoembryonic Antigen/immunology , Epitopes/analysis , Antibodies, Monoclonal , Humans , Lectins , Radioimmunoassay
11.
Arch Dermatol Res ; 279(8): 550-7, 1987.
Article in English | MEDLINE | ID: mdl-3435182

ABSTRACT

The expression of MAM-3 and MAM-6 antigens was immunohistochemically investigated on 110 tumors of human skin appendages. Forty-two samples from tumor-adjacent normal skin appendages were also studied. MAM-3 antigens, as detectable by monoclonal antibodies (MoAbs) 67D11, 115G3, and 115H10 were present in the inner layer cells but not in the outer layer cells of normal eccrine excretory ducts. Sporadic positivity was also found in cytoplasm of apocrine acini with 115G3, while 67D11 and 115H10 were negative. MAM-6 antigens, as detectable by the MoAbs 115D8, 115F5, 139H2, 140C1, and 126E7 were found in the secretory canaliculi of normal eccrine acini and within the apical lumina at the terminal portion of ducts. Apocrine acinar cells mainly exhibited an apical staining, but a focal supranuclear dot-like staining could also be observed. A foamy reaction pattern for MAM-6 was noted in mature sebocytes. However, none of the antigenic epitopes was expressed in normal squamous epithelium or hair follicles. In benign tumors, the staining patterns for both antigens, in general, resembled their distribution in the corresponding normal tissues. However, carcinomas originating from sweat glands, sebaceous glands, and the pilar apparatus expressed both antigens in a more irregular and heterogeneous pattern. This might preferably be explained by the loss of those mechanisms controlling the antigen expression in mature, functional tissues. Conclusions from these immunohistochemical studies with regard to the histogenesis mainly of the malignant skin appendage tumors should be drawn with caution.


Subject(s)
Antigens/analysis , Membrane Glycoproteins/analysis , Skin Diseases/immunology , Skin Neoplasms/immunology , Skin/immunology , Antibodies, Monoclonal , Humans , Immunohistochemistry , Mucin-1 , Skin Diseases/pathology , Skin Neoplasms/pathology
12.
Zentralbl Allg Pathol ; 132(3): 193-6, 1986.
Article in German | MEDLINE | ID: mdl-2431555

ABSTRACT

Chordomas are rare slow-growing but locally invasive tumors. They are thought to develop from residues of the notochord. Three chordomas and ten chondroid tumors were investigated by an indirect immunoperoxidase method for expression of the epithelial markers: MAM-6, keratin, tissue polypeptide antigen (TPA) and for carcinoembryonic antigen (CEA). In all the chordomas investigated the antigens MAM-6, keratin and TPA were detected using monoclonal antibodies and conventional antisera, respectively. These data provide further evidence of the epithelial nature and the ectodermal origin of chordomas. Moreover, the findings suggest that immunohistochemical methods may be useful for the differential diagnosis between chordomas and morphologically similar chondroid tumors.


Subject(s)
Bone Neoplasms/analysis , Chondrosarcoma/analysis , Chordoma/analysis , Osteosarcoma/analysis , Antibodies, Monoclonal , Bone Neoplasms/diagnosis , Carcinoembryonic Antigen/analysis , Chondrosarcoma/diagnosis , Chordoma/diagnosis , Coccyx , Diagnosis, Differential , Humans , Immune Sera , Immunoenzyme Techniques , Keratins/analysis , Lumbar Vertebrae , Membrane Proteins/analysis , Mucin-1 , Osteosarcoma/diagnosis , Peptides/analysis , Sphenoid Bone , Spinal Neoplasms/analysis , Tissue Polypeptide Antigen
13.
Zentralbl Allg Pathol ; 132(3): 233-42, 1986.
Article in German | MEDLINE | ID: mdl-3788316

ABSTRACT

Tissue samples of 9 leukoplakias, 19 oral squamous cell carcinomas, 9 basaliomas and 6 specimens of normal oral mucosa were labeled with 3H-thymidine using an in vitro technique; the size of the S-phase fraction was determined histoautoradiographically. Whereas leukoplakias (with or without dysplasia) showed an homogeneous growth pattern, carcinomas and basaliomas demonstrated significantly higher proliferative activity in the tumor periphery. In the basaliomas the pallisade cells showed significantly higher indices than the polygonal cells. The proliferative potential of the oral squamous cell carcinomas is high compared to other neoplasias and depends on the grade and type of growth. The epithelial marker MAM-6 detected immunohistologically on the same tissue, showed a stronger expression in oral carcinomas than in leukoplakias. A direct relationship between the intensity of antigen expression and the proliferative behaviour (size of the S-phase fraction) was not detectable.


Subject(s)
Facial Neoplasms/analysis , Membrane Proteins/analysis , Mouth Neoplasms/analysis , Adult , Aged , Aged, 80 and over , Autoradiography , Carcinoma, Basal Cell/analysis , Carcinoma, Basal Cell/pathology , Carcinoma, Squamous Cell/analysis , Carcinoma, Squamous Cell/pathology , Cell Division , Facial Neoplasms/pathology , Female , Humans , Interphase , Kinetics , Leukoplakia, Oral/analysis , Leukoplakia, Oral/pathology , Male , Middle Aged , Mouth Neoplasms/pathology , Mucin-1
14.
Zentralbl Allg Pathol ; 132(3): 253-65, 1986.
Article in German | MEDLINE | ID: mdl-3788318

ABSTRACT

For all persons who died in the city of Dresden and 7 surrounding counties from 1967 to 1978, documents relating to the clinical and pathologic diagnosis were examined and findings compared. The study covered nearly two thirds of all deaths which occurred in the district of Dresden during this time period. The autopsy rate overall was found to be 22.8%. In 57.3% the clinical diagnoses were found to have been correct, in 19.7% they corresponded in part, but in 23% there was no concordance whatsoever between the clinical and autopsy diagnoses. The influence of age, place of death and disease group on the agreement between clinical and underlying pathoanatomic diagnosis was also examined. The analysis highlighted the degree to which death statistics based on the death certificate are misleading. In up to 28.8% of cases there were formal errors in the underlying disease diagnosis listed by the certifying physician on the death certificate. The value of regular comparison between the diagnoses, and its usefulness for training and continuing medical education are emphasized. The results of the study underline the importance of making available more prospectors in the district of Dresden to meet the expanding tasks of the clinically active pathologist in autopsy and biopsy diagnostic efforts.


Subject(s)
Autopsy , Diagnostic Errors , Death Certificates , Education, Medical , Germany, East , Humans , Quality Assurance, Health Care
15.
Zentralbl Allg Pathol ; 132(3): 181-91, 1986.
Article in German | MEDLINE | ID: mdl-3538705

ABSTRACT

Our experience with the demonstration of tissue markers in histopathology supports their value in differential diagnosis of routine material. Microscopic diagnostic methods are genuinely enriched by the use of such monoclonal antibodies and conventional antisera whose specificity has been adequately demonstrated using indirect peroxidase techniques in cut sections and on cytologic preparations. On the basis of several epithelial markers (carcinoembryonic antigen, keratin, tissue polypeptide antigen, MAM-antigens) and other antigens (protein S-100, chromogranin) examples are given for their application to routine differential diagnosis problems. The detection of these markers has been adapted to standardized indirect immunoperoxidase techniques. More sensitive tissue markers (i.e. antigens which do not withstand formalin fixation and paraffin embedding) should best be dealt with by specialized working groups.


Subject(s)
Antibodies, Monoclonal , Immune Sera , Immunoenzyme Techniques , Animals , Antibody Specificity , Diagnosis, Differential , Humans
16.
Article in English | MEDLINE | ID: mdl-2988188

ABSTRACT

About 200 human tumours and corresponding normal tissue samples were investigated by immunoperoxidase tests for the expression of MAM-3, MAM-5 and MAM-6 antigens, which had previously been defined by monoclonal antibodies to human milk fat globule membranes. All tissue specimens had been treated for routine histopathology, i.e. fixed in formalin and embedded in paraffin. One of the antigens, MAM-6, appeared to be an important epithelial marker, present in all normal and neoplastic breast tissue samples, in about 80% of non-mammary normal tissues and in more than 90% of non-mammary epithelial tumours. It could never be detected in normal and neoplastic mesenchymal and neuroectodermal structures. Direct comparison with the distribution of Carcinoembryonic Antigen (CEA), Tissue Polypeptide Antigen (TPA) and keratin provided clear evidence that MAM-6 is different from these well known epithelial markers. MAM-3 proved to be an additional important marker exhibiting a characteristic distribution pattern in those epithelial tissues investigated. In contrast to MAM-6, it could never be detected in renal cell cancers and carcinomas of the prostate gland, thus allowing differential diagnosis on the basis of immunohistochemistry. MAM-5, known to be associated with lactoferrin, was mainly detectable in secretory organs and their tumours. In the group of breast tumours, its expression was mainly seen in lobular cancers. These findings suggest a use for these new markers for routine histopathology.


Subject(s)
Antibodies, Monoclonal , Antigens, Surface/immunology , Histological Techniques , Membrane Proteins/immunology , Adenocarcinoma/immunology , Breast/immunology , Breast Neoplasms/immunology , Carcinoma/immunology , Carcinoma, Intraductal, Noninfiltrating/immunology , Epithelium/immunology , Female , Histocytochemistry , Humans , Immunochemistry , Mucin-1 , Neoplasms/immunology
17.
Arch Geschwulstforsch ; 54(1): 1-12, 1984.
Article in English | MEDLINE | ID: mdl-6200086

ABSTRACT

Experience is described in applying monoclonal antibodies (Mabs) to immunohistology, epitope analysis on antigens, and radioimmunoassay. The antibodies (provided by international laboratories) used in the experiments described were directed to the mouse mammary tumor virus, a cell surface component of melanoma cells, several proteins of the human milk fat globule membrane (as markers for cell differentiation in breast cancers) as well as to Carcinoembryonic Antigen (CEA). At least three antigenic determinants were detected on CEA, which appeared as being expressed in different quantities in those organs producing CEA-like molecules (lung, spleen, normal colon mucosa, liver). By means of an inhibition radioimmunoassay for CEA, evidence was obtained that in the lung more than one cross-reacting antigen might exist, one of them of high molecular weight (about or more than 200,000 daltons). In immunoperoxidase tests, several antibodies to CEA were seen to react with pulmocytes and bronchus glands. Summarizing the experience, it is concluded that thorough characterization of monoclonal antibodies by more than one method is a prerequisite to their use for analytical or diagnostic purpose.


Subject(s)
Antibodies, Monoclonal/immunology , Antigens, Neoplasm/immunology , Animals , Antibody Specificity , Antigens/immunology , Antigens, Viral/immunology , Carcinoembryonic Antigen/immunology , Cross Reactions , Epitopes/immunology , Fluorescent Antibody Technique , Humans , Immunoassay , Immunoenzyme Techniques , Mammary Tumor Virus, Mouse/immunology , Melanoma/immunology , Membrane Proteins/immunology , Mice , Mucin-1 , Radioimmunoassay
18.
Eur J Cancer Clin Oncol ; 19(10): 1421-9, 1983 Oct.
Article in English | MEDLINE | ID: mdl-6685630

ABSTRACT

By means of the macrophage electrophoretic mobility technique a striking digestive system cancer-associated human lymphocyte response to CEA has been found during a large-scale study including tests in 499 individuals. The question to be answered by this study was whether this response is really CEA-specific. Titration experiments with 3 different CEA preparations in lymphocytes from 5 colorectal cancer patients showed that the threshold dose of CEA necessary to induce lymphocyte responses amounts to 50-100 ng CEA per ml and 10(6) lymphocytes, regardless of the CEA origin and its state of purity. The CEA specificity of the responses was proved by neutralization experiments with 3 CEA-specific monoclonal antibodies. When allowed to react with CEA before lymphocyte incubation, the MABs prevented CEA from inducing lymphocyte responses. Appropriate murine control myeloma protein did not influence these responses. The reactivity of these lymphocyte samples to a teratocarcinoma extract could not be prevented by treating this material with CEA-specific MABs before incubation. Preliminary attempts to enrich the lymphokine(s) released after CEA stimulation resulted in recovery of the activity within 2 arbitrarily cut Sephadex G-100 fractions comprising the mol. wt range of 3000-47,000.


Subject(s)
Antibodies, Monoclonal/immunology , Carcinoembryonic Antigen/immunology , Lymphocyte Activation , Cell Migration Inhibition , Colonic Neoplasms/immunology , Dose-Response Relationship, Immunologic , Female , Humans , Lymphokines/analysis , Macrophages/immunology , Neutralization Tests , Pregnancy , Rectal Neoplasms/immunology
19.
Int J Cancer ; 32(1): 27-35, 1983 Jul 15.
Article in English | MEDLINE | ID: mdl-6305853

ABSTRACT

Human IgG antibodies reacting in the indirect immunofluorescence test with clusters of intracytoplasmic A particles in mouse tissues were analyzed by means of both radioimmunoprecipitation and enzyme-linked immunoabsorbant assays. Generally, antibody-containing sera reacted with epitopes of p14, the nucleic-acid-binding core protein of mouse mammary tumor virus, corresponding to the protein Ap14 of intracytoplasmic A particles. Comparatively few sera reacted with epitopes of the main core protein p28 corresponding to the protein Ap28 of intracytoplasmic A particles. The two types of reactivity occurred independently of each other.


Subject(s)
Immunoglobulin G/immunology , Inclusion Bodies, Viral/immunology , Mammary Tumor Virus, Mouse/immunology , Viral Proteins/immunology , Cell Line , Enzyme-Linked Immunosorbent Assay , Fluorescent Antibody Technique , Humans
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